Steven Chu

All Publications

• Noninvasive virtual biopsy using micro-registered optical coherence tomography (OCT) in human subjects. Science advances Winetraub, Y., Van Vleck, A., Yuan, E., Terem, I., Zhao, J., Yu, C., Chan, W., Do, H., Shevidi, S., Mao, M., Yu, J., Hong, M., Blankenberg, E., Rieger, K. E., Chu, S., Aasi, S., Sarin, K. Y., de la Zerda, A. 2024; 10 (15): eadi5794

  Abstract

  Histological hematoxylin and eosin-stained (H&E) tissue sections are used as the gold standard for pathologic detection of cancer, tumor margin detection, and disease diagnosis. Producing H&E sections, however, is invasive and time-consuming. While deep learning has shown promise in virtual staining of unstained tissue slides, true virtual biopsy requires staining of images taken from intact tissue. In this work, we developed a micron-accuracy coregistration method [micro-registered optical coherence tomography (OCT)] that can take a two-dimensional (2D) H&E slide and find the exact corresponding section in a 3D OCT image taken from the original fresh tissue. We trained a conditional generative adversarial network using the paired dataset and showed high-fidelity conversion of noninvasive OCT images to virtually stained H&E slices in both 2D and 3D. Applying these trained neural networks to in vivo OCT images should enable physicians to readily incorporate OCT imaging into their clinical practice, reducing the number of unnecessary biopsy procedures.

  View details for DOI 10.1126/sciadv.adi5794

  View details for PubMedID 38598626

  View details for PubMedCentralID PMC11006228

• Trends of extreme US weather events in the changing climate. Proceedings of the National Academy of Sciences of the United States of America Shenoy, S., Gorinevsky, D., Trenberth, K. E., Chu, S. 2022; 119 (47): e2207536119

  Abstract

  Trends in extreme 100-y events of temperature and rainfall amounts in the continental United States are estimated, to see effects of climate change. This is a nontrivial statistical problem because climate change effects have to be extracted from "noisy" weather data within a limited time range. We use nonparametric Bayesian methods to estimate the trends of extreme events that have occurred between 1979 and 2019, based on data for temperature and rainfall. We focus on 100-y events for each month in [Formula: see text] geographical areas looking at hourly temperature and 5-d cumulative rainfall. Distribution tail models are constructed using extreme value theory (EVT) and data on 33-y events. This work shows it is possible to aggregate data from spatial points in diverse climate zones for a given month and fit an EVT model with the same parameters. This surprising result means there are enough extreme event data to see the trends in the 41-y record for each calendar month. The yearly trends of the risk of a 100-y high-temperature event show an average 2.1-fold increase over the last 41 y of data across all months, with a 2.6-fold increase for the months of July through October. The risk of high rainfall extremes increases in December and January 1.4-fold, but declines by 22% for the spring and summer months.

  View details for DOI 10.1073/pnas.2207536119

  View details for PubMedID 36375064

• Reversibly Photoswitching Upconversion Nanoparticles for Super-sensitive Photoacoustic Molecular Imaging. Angewandte Chemie (International ed. in English) Rao, J., Liu, C., Zheng, X., Dai, T., Wang, H., Chen, X., Chen, B., Sun, T., Wang, F., Chu, S. 2022

  Abstract

  Photoacoustic (PA) imaging uses light excitation to generate the acoustic signal for detection and improves tissue penetration depth and spatial resolution in the clinically relevant depth of living subjects. However, strong background signals from blood and pigments have significantly compromised the sensitivity of PA imaging with exogenous contrast agents. Here we report a nanoparticle-based probe design that uses light to reversibly modulate the PA emission to enable photoacoustic photoswitching imaging (PAPSI) in living mice. Such a nanoprobe is built with upconverting nanocrystals and photoswitchable small molecules and can be switched on by NIR light through upconversion to UV energy. Reversibly photoswitching of the nanoprobe reliably removed strong tissue background, increased the contrast-to-noise ratio, and thus improved imaging sensitivity. We have shown that PAPSI can image 0.05 nM of the nanoprobe in hemoglobin solution and 10 4 labeled cancer cells after implantation in living mice using a commercial PA imager.

  View details for DOI 10.1002/anie.202116802

  View details for PubMedID 35139242

• Engineering Bright and Mechanosensitive Alkaline-Earth Rare-Earth Upconverting Nanoparticles. The journal of physical chemistry letters McLellan, C. A., Siefe, C., Casar, J. R., Peng, C. S., Fischer, S., Lay, A., Parakh, A., Ke, F., Gu, X. W., Mao, W., Chu, S., Goodman, M. B., Dionne, J. A. 2022: 1547-1553

  Abstract

  Upconverting nanoparticles (UCNPs) are an emerging platform for mechanical force sensing at the nanometer scale. An outstanding challenge in realizing nanometer-scale mechano-sensitive UCNPs is maintaining a high mechanical force responsivity in conjunction with bright optical emission. This Letter reports mechano-sensing UCNPs based on the lanthanide dopants Yb3+ and Er3+, which exhibit a strong ratiometric change in emission spectra and bright emission under applied pressure. We synthesize and analyze the pressure response of five different types of nanoparticles, including cubic NaYF4 host nanoparticles and alkaline-earth host materials CaLuF, SrLuF, SrYbF, and BaLuF, all with lengths of 15 nm or less. By combining optical spectroscopy in a diamond anvil cell with single-particle brightness, we determine the noise equivalent sensitivity (GPa/√Hz) of these particles. The SrYb0.72Er0.28F@SrLuF particles exhibit an optimum noise equivalent sensitivity of 0.26 ± 0.04 GPa/√Hz. These particles present the possibility of robust nanometer-scale mechano-sensing.

  View details for DOI 10.1021/acs.jpclett.1c03841

  View details for PubMedID 35133831

• PERSONAL PROTECTIVE EQUIPMENT (PPE) SEES THE LIGHT: LOW-COST METHYLENE BLUE PLUS LIGHT INACTIVATES SARS-COV-2 ON PPE INCLUDING MASKS AND RESPIRATORS Lendvay, T. S., Chen, J., Harcourt, B. H., Scholte, F. E., Kilinc-Balci, F., Lin, Y., Lamb, M. M., Chu, L. C., Evans, D., Price, A., Lin, Y., Mores, C. N., Sahni, J., Kabra, K., Haubruge, E., Thiry, E., Heyne, B., Laperre, J., Simmons, S., Cui, Y., Wagner, T., Clark, T., Smit, S., Parker, R., Gallagher, T., Timm, E., Ludwig-Begall, L., Ludwig-Begall, L., Macia, N., Mackie, C., Page, K., Reader, S., Farris, P., Jolois, O., Patel, A., Lemyre, J., Molloy-Simard, V., Homdayjanakul, K., Tritsch, S., Wielick, C., Mayo, M., Malott, R., Willaert, J., Nauwynck, H., Dams, L., De Jaeger, S., Lao, L., Zhao, M., Chu, S., Conly, J. M., Chu, M. C. AMER SOC TROP MED & HYGIENE. 2021: 8

  View details for Web of Science ID 000778105601023

• Single Particle Cathodoluminescence Spectroscopy with Sub-20 nm, Electron-Stable Phosphors ACS PHOTONICS Swearer, D. F., Fischer, S., Angell, D. K., Siefe, C., Alivisatos, A., Chu, S., Dionne, J. A. 2021; 8 (6): 1539-1547

  View details for DOI 10.1021/acsphotonics.1c00235

  View details for Web of Science ID 000664306400004

• Addressing Personal Protective Equipment (PPE) Decontamination: Methylene Blue and Light Inactivates SARS-CoV-2 on N95 Respirators and Medical Masks with Maintenance of Integrity and Fit. Infection control and hospital epidemiology Lendvay, T. S., Chen, J., Harcourt, B. H., Scholte, F. E., Lin, Y. L., Kilinc-Balci, F. S., Lamb, M. M., Homdayjanakul, K., Cui, Y., Price, A., Heyne, B., Sahni, J., Kabra, K. B., Lin, Y., Evans, D., Mores, C. N., Page, K., Chu, L. F., Haubruge, E., Thiry, E., Ludwig-Begall, L. F., Wielick, C., Clark, T., Wagner, T., Timm, E., Gallagher, T., Faris, P., Macia, N., Mackie, C. J., Simmons, S. M., Reader, S., Malott, R., Hope, K., Davies, J. M., Tritsch, S. R., Dams, L., Nauwynck, H., Willaert, J., De Jaeger, S., Liao, L., Zhao, M., Laperre, J., Jolois, O., Smit, S. J., Patel, A. N., Mayo, M., Parker, R., Molloy-Simard, V., Lemyre, J., Chu, S., Conly, J. M., Chu, M. C. 2021: 1-83

  Abstract

  OBJECTIVE: The coronavirus disease 2019 (COVID-19) pandemic has resulted in shortages of personal protective equipment (PPE) underscoring the urgent need for simple, efficient, and inexpensive methods to decontaminate SARS-CoV-2-exposed masks and respirators. We hypothesized that methylene blue (MB) photochemical treatment, which has various clinical applications, could decontaminate PPE contaminated with coronavirus.DESIGN: The two arms of the study included: 1) PPE inoculation with coronaviruses followed by MB with light (MBL) decontamination treatment, and 2) PPE treatment with MBL for 5 cycles of decontamination (5CD) to determine maintenance of PPE performance.METHODS: MBL treatment was used to inactivate coronaviruses on three N95 filtering facepiece respirator (FFR) and two medical mask (MM) models. We inoculated FFR and MM materials with three coronaviruses, including SARS-CoV-2, and treated with 10 M MB and exposed to 50,000 lux of white light or 12,500 lux of red light for 30 minutes. In parallel, integrity was assessed after 5CD using multiple US and international test methods and compared to the FDA-authorized vaporized hydrogen peroxide plus ozone (VHP+O3) decontamination method.RESULTS: Overall, MBL robustly and consistently inactivated all three coronaviruses with 99.8 - to >99.9% virus inactivation across all FFRs and MMs tested. FFR and MM integrity was maintained after 5 cycles of MBL treatment, whereas one FFR model failed after 5 cycles of VHP+O3.CONCLUSIONS: MBL treatment decontaminated respirators and masks by inactivating three tested coronaviruses without compromising integrity through 5CD. MBL decontamination is effective, low-cost and does not require specialized equipment, making it applicable in all-resource settings.

  View details for DOI 10.1017/ice.2021.230

  View details for PubMedID 34016200

• Three-Dimensional Analysis of Particle Distribution on Filter Layers inside N95 Respirators by Deep Learning. Nano letters Lee, H. R., Liao, L., Xiao, W., Vailionis, A., Ricco, A. J., White, R., Nishi, Y., Chiu, W., Chu, S., Cui, Y. 2020

  Abstract

  The global COVID-19 pandemic has changed many aspects of daily lives. Wearing personal protective equipment, especially respirators (face masks), has become common for both the public and medical professionals, proving to be effective in preventing spread of the virus. Nevertheless, a detailed understanding of respirator filtration-layer internal structures and their physical configurations is lacking. Here, we report three-dimensional (3D) internal analysis of N95 filtration layers via X-ray tomography. Using deep learning methods, we uncover how the distribution and diameters of fibers within these layers directly affect contaminant particle filtration. The average porosity of the filter layers is found to be 89.1%. Contaminants are more efficiently captured by denser fiber regions, with fibers <1.8 mum in diameter being particularly effective, presumably because of the stronger electric field gradient on smaller diameter fibers. This study provides critical information for further development of N95-type respirators that combine high efficiency with good breathability.

  View details for DOI 10.1021/acs.nanolett.0c04230

  View details for PubMedID 33283521

• Obituary Arthur Ashkin (1922-2020) NATURE Chu, S. 2020; 588 (7836): 29

  View details for DOI 10.1038/d41586-020-03380-4

  View details for Web of Science ID 000594830100005

• Lithium Extraction from Seawater through Pulsed Electrochemical Intercalation JOULE Liu, C., Li, Y., Lin, D., Hsu, P., Liu, B., Yan, G., Wu, T., Cui, Y., Chu, S. 2020; 4 (7): 1459–69

  View details for DOI 10.1016/j.joule.2020.05.017

  View details for Web of Science ID 000551427400014

• Household Materials Selection for Homemade Cloth Face Coverings and Their Filtration Efficiency Enhancement with Triboelectric Charging. Nano letters Zhao, M., Liao, L., Xiao, W., Yu, X., Wang, H., Wang, Q., Lin, Y. L., Kilinc-Balci, F. S., Price, A., Chu, L., Chu, M. C., Chu, S., Cui, Y. 2020

  Abstract

  The COVID-19 pandemic is currently causing a severe disruption and shortage in the global supply chain of necessary personal protective equipment (e.g., N95 respirators). The U.S. CDC has recommended use of household cloth by the general public to make cloth face coverings as a method of source control. We evaluated the filtration properties of natural and synthetic materials using a modified procedure for N95 respirator approval. Common fabrics of cotton, polyester, nylon, and silk had filtration efficiency of 5-25%, polypropylene spunbond had filtration efficiency 6-10%, and paper-based products had filtration efficiency of 10-20%. An advantage of polypropylene spunbond is that it can be simply triboelectrically charged to enhance the filtration efficiency (from 6 to >10%) without any increase in pressure (stable overnight and in humid environments). Using the filtration quality factor, fabric microstructure, and charging ability, we are able to provide an assessment of suggested fabric materials for homemade facial coverings.

  View details for DOI 10.1021/acs.nanolett.0c02211

  View details for PubMedID 32484683

• Can N95 Respirators Be Reused after Disinfection? How Many Times? ACS nano Liao, L., Xiao, W., Zhao, M., Yu, X., Wang, H., Wang, Q., Chu, S., Cui, Y. 2020

  Abstract

  The coronavirus disease 2019 (COVID-19) pandemic has led to a major shortage of N95 respirators, which are essential for protecting healthcare professionals and the general public who may come into contact with the virus. Thus, it is essential to determine how we can reuse respirators and other personal protective equipment in these urgent times. We investigated multiple commonly used disinfection schemes on media with particle filtration efficiency of 95%. Heating was recently found to inactivate the virus in solution within 5 min at 70 °C and is among the most scalable, user-friendly methods for viral disinfection. We found that heat (≤85 °C) under various humidities (≤100% relative humidity, RH) was the most promising, nondestructive method for the preservation of filtration properties in meltblown fabrics as well as N95-grade respirators. At 85 °C, 30% RH, we were able to perform 50 cycles of heat treatment without significant changes in the filtration efficiency. At low humidity or dry conditions, temperatures up to 100 °C were not found to alter the filtration efficiency significantly within 20 cycles of treatment. Ultraviolet (UV) irradiation was a secondary choice, which was able to withstand 10 cycles of treatment and showed small degradation by 20 cycles. However, UV can potentially impact the material strength and subsequent sealing of respirators. Finally, treatments involving liquids and vapors require caution, as steam, alcohol, and household bleach all may lead to degradation of the filtration efficiency, leaving the user vulnerable to the viral aerosols.

  View details for DOI 10.1021/acsnano.0c03597

  View details for PubMedID 32368894

• Difference-Frequency Ultrasound Imaging With Non-Linear Contrast IEEE TRANSACTIONS ON MEDICAL IMAGING Li, Y., Polyak, D., Johnson, E., Yecies, D., Shevidi, S., de la Zerda, A., Gephart, M., Chu, S. 2020; 39 (5): 1759–66

  Abstract

  Conventional ultrasound imaging is based on the scattering of sound from inhomogeneities in the density and the speed of sound and is often used in medicine to resolve pathologic compared to normal tissue. Here we demonstrate a difference-frequency ultrasound (dfUS) imaging method that is based on the interaction of two sound pulses that propagate non-collinearly and intersect in space and time. The dfUS signal arises primarily from the second-order non-linear coefficient, a contrast mechanism that differs from linear and harmonic US imaging. The distinct contrast mechanism allows dfUS to image anatomic features that are not identifiable in conventional US images of salmon and pig kidney tissue. Further, dfUS produces enhanced contrast of glioblastoma tumor implanted in the mouse brain, revealing its potential for improving medical diagnosis. Progress towards a real-time system is discussed.

  View details for DOI 10.1109/TMI.2019.2957280

  View details for Web of Science ID 000532214700043

  View details for PubMedID 31804930

• Tackling the grand challenges PHYSICS WORLD Chu, S., Blaustein, R. 2020; 33 (3): 13

  View details for Web of Science ID 000546424900010

• Single-particle spectroscopy for functional nanomaterials. Nature Zhou, J., Chizhik, A. I., Chu, S., Jin, D. 2020; 579 (7797): 41–50

  Abstract

  Tremendous progress in nanotechnology has enabled advances in the use of luminescent nanomaterials in imaging, sensing and photonic devices. This translational process relies on controlling the photophysical properties of the building block, that is, single luminescent nanoparticles. In this Review, we highlight the importance of single-particle spectroscopy in revealing the diverse optical properties and functionalities of nanomaterials, and compare it with ensemble fluorescence spectroscopy. The information provided by this technique has guided materials science in tailoring the synthesis of nanomaterials to achieve optical uniformity and to develop novel applications. We discuss the opportunities and challenges that arise from pushing the resolution limit, integrating measurement and manipulation modalities, and establishing the relationship between the structure and functionality of single nanoparticles.

  View details for DOI 10.1038/s41586-020-2048-8

  View details for PubMedID 32132689

• Synergistic enhancement of electrocatalytic CO2 reduction to C2 oxygenates at nitrogen-doped nanodiamonds/Cu interface. Nature nanotechnology Wang, H., Tzeng, Y., Ji, Y., Li, Y., Li, J., Zheng, X., Yang, A., Liu, Y., Gong, Y., Cai, L., Li, Y., Zhang, X., Chen, W., Liu, B., Lu, H., Melosh, N. A., Shen, Z., Chan, K., Tan, T., Chu, S., Cui, Y. 2020

  Abstract

  To date, effective control over the electrochemical reduction of CO2 to multicarbon products (C≥2) has been very challenging. Here, we report a design principle for the creation of a selective yet robust catalytic interface for heterogeneous electrocatalysts in the reduction of CO2 to C2 oxygenates, demonstrated by rational tuning of an assembly of nitrogen-doped nanodiamonds and copper nanoparticles. The catalyst exhibits a Faradaic efficiency of ~63% towards C2 oxygenates at applied potentials of only -0.5V versus reversible hydrogen electrode. Moreover, this catalyst shows an unprecedented persistent catalytic performance up to 120h, with steady current and only 19% activity decay. Density functional theory calculations show that CO binding is strengthened at the copper/nanodiamond interface, suppressing CO desorption and promoting C2 production by lowering the apparent barrier for CO dimerization. The inherent compositional and electronic tunability of the catalyst assembly offers an unrivalled degree of control over the catalytic interface, and thereby the reaction energetics and kinetics.

  View details for DOI 10.1038/s41565-019-0603-y

  View details for PubMedID 31907442

• Electrochemical generation of liquid and solid sulfur on two-dimensional layered materials with distinct areal capacities. Nature nanotechnology Yang, A. n., Zhou, G. n., Kong, X. n., Vilá, R. A., Pei, A. n., Wu, Y. n., Yu, X. n., Zheng, X. n., Wu, C. L., Liu, B. n., Chen, H. n., Xu, Y. n., Chen, D. n., Li, Y. n., Fakra, S. n., Hwang, H. Y., Qin, J. n., Chu, S. n., Cui, Y. n. 2020

  Abstract

  It has recently been shown that sulfur, a solid material in its elementary form S8, can stay in a supercooled state as liquid sulfur in an electrochemical cell. We establish that this newly discovered state could have implications for lithium-sulfur batteries. Here, through in situ studies of electrochemical sulfur generation, we show that liquid (supercooled) and solid elementary sulfur possess very different areal capacities over the same charging period. To control the physical state of sulfur, we studied its growth on two-dimensional layered materials. We found that on the basal plane, only liquid sulfur accumulates; by contrast, at the edge sites, liquid sulfur accumulates if the thickness of the two-dimensional material is small, whereas solid sulfur nucleates if the thickness is large (tens of nanometres). Correlating the sulfur states with their respective areal capacities, as well as controlling the growth of sulfur on two-dimensional materials, could provide insights for the design of future lithium-sulfur batteries.

  View details for DOI 10.1038/s41565-019-0624-6

  View details for PubMedID 31988508

• A Single-Molecule Surface-Based Platform to Detect the Assembly and Function of the Human RNA Polymerase II Transcription Machinery. Structure (London, England : 1993) Park, S. R., Hauver, J. n., Zhang, Y. n., Revyakin, A. n., Coleman, R. A., Tjian, R. n., Chu, S. n., Pertsinidis, A. n. 2020

  Abstract

  Single-molecule detection and manipulation is a powerful tool for unraveling dynamic biological processes. Unfortunately, success in such experiments is often challenged by tethering the biomolecule(s) of interest to a biocompatible surface. Here, we describe a robust surface passivation method by dense polymer brush grafting, based on optimized polyethylene glycol (PEG) deposition conditions, exactly at the lower critical point of an aqueous biphasic PEG-salt system. The increased biocompatibility achieved, compared with PEG deposition in sub-optimal conditions away from the critical point, allowed us to successfully detect the assembly and function of a large macromolecular machine, a fluorescent-labeled multi-subunit, human RNA Polymerase II Transcription Pre-Initiation Complex, on single, promoter-containing, surface-immobilized DNA molecules. This platform will enable probing the complex biochemistry and dynamics of large, multi-subunit macromolecular assemblies, such as during the initiation of human RNA Pol II transcription, at the single-molecule level.

  View details for DOI 10.1016/j.str.2020.07.009

  View details for PubMedID 32763141

• A scalable method of applying heat and humidity for decontamination of N95 respirators during the COVID-19 crisis. PloS one Anderegg, L., Meisenhelder, C., Ngooi, C. O., Liao, L., Xiao, W., Chu, S., Cui, Y., Doyle, J. M. 2020; 15 (7): e0234851

  Abstract

  A lack of N95 Filtering Facepiece Respirators (FFRs) during the COVID-19 crisis has placed healthcare workers at risk. It is important for any N95 reuse strategy to determine the effects that proposed protocols would have on the physical functioning of the mask, as well as the practical aspects of implementation. Here we propose and implement a method of heating N95 respirators with moisture (85°C, 60-85% humidity). We test both mask filtration efficiency and fit to validate this process. Our tests focus on the 3M 1860, 3M 1870, and 3M 8210 Plus N95 models. After five cycles of the heating procedure, all three respirators pass both quantitative fit testing (score of >100) and show no degradation of mask filtration efficiency. We also test the Chen Heng V9501 KN95 and HKYQ N95 finding no degradation of mask filtration efficiency, however even for unheated masks these scored <50 for every fit test. The heating method presented here is scalable from individual masks to over a thousand a day with a single industrial convection oven, making this method practical for local application inside health-care facilities.

  View details for DOI 10.1371/journal.pone.0234851

  View details for PubMedID 32609741

• A Core-Shell-Shell Nanoparticle Architecture Towards Bright Upconversion and Improved Forster Resonant Energy Transfer Siefe, C., Mehlenbacher, R. D., Peng, C., Zhang, Y., Fischer, S., Lay, A., McLellan, C. A., Alivisatos, A., Chu, S., Dionne, J. A., IEEE IEEE. 2020

  View details for Web of Science ID 000612090002272

• Electrochemical generation of liquid and solid sulfur on two-dimensional layered materials with distinct areal capacities Nature Nanotechnology Yang, A., Zhou, G., et al 2020

  View details for DOI 10.1038/s41565-019-0624-6

• Decontamination of SARS-CoV-2 and Other RNA Viruses from N95 Level Meltblown Polypropylene Fabric Using Heat under Different Humidities. ACS nano Campos, R. K., Jin, J. n., Rafael, G. H., Zhao, M. n., Liao, L. n., Simmons, G. n., Chu, S. n., Weaver, S. C., Chiu, W. n., Cui, Y. n. 2020

  Abstract

  In March of 2020, the World Health Organization declared a pandemic of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The pandemic led to a shortage of N95-grade filtering facepiece respirators (FFRs), especially surgical-grade N95 FFRs for protection of healthcare professionals against airborne transmission of SARS-CoV-2. We and others have previously reported promising decontamination methods that may be applied to the recycling and reuse of FFRs. In this study we tested disinfection of three viruses, including SARS-CoV-2, dried on a piece of meltblown fabric, the principal component responsible for filtering of fine particles in N95-level FFRs, under a range of temperatures (60-95 °C) at ambient or 100% relative humidity (RH) in conjunction with filtration efficiency testing. We found that heat treatments of 75 °C for 30 min or 85 °C for 20 min at 100% RH resulted in efficient decontamination from the fabric of SARS-CoV-2, human coronavirus NL63 (HCoV-NL63), and another enveloped RNA virus, chikungunya virus vaccine strain 181/25 (CHIKV-181/25), without lowering the meltblown fabric's filtration efficiency.

  View details for DOI 10.1021/acsnano.0c06565

  View details for PubMedID 32955847

• Electrotunable liquid sulfur microdroplets. Nature communications Zhou, G. n., Yang, A. n., Wang, Y. n., Gao, G. n., Pei, A. n., Yu, X. n., Zhu, Y. n., Zong, L. n., Liu, B. n., Xu, J. n., Liu, N. n., Zhang, J. n., Li, Y. n., Wang, L. W., Hwang, H. Y., Brongersma, M. L., Chu, S. n., Cui, Y. n. 2020; 11 (1): 606

  Abstract

  Manipulating liquids with tunable shape and optical functionalities in real time is important for electroactive flow devices and optoelectronic devices, but remains a great challenge. Here, we demonstrate electrotunable liquid sulfur microdroplets in an electrochemical cell. We observe electrowetting and merging of sulfur droplets under different potentiostatic conditions, and successfully control these processes via selective design of sulfiphilic/sulfiphobic substrates. Moreover, we employ the electrowetting phenomena to create a microlens based on the liquid sulfur microdroplets and tune its characteristics in real time through changing the shape of the liquid microdroplets in a fast, repeatable, and controlled manner. These studies demonstrate a powerful in situ optical battery platform for unraveling the complex reaction mechanism of sulfur chemistries and for exploring the rich material properties of the liquid sulfur, which shed light on the applications of liquid sulfur droplets in devices such as microlenses, and potentially other electrotunable and optoelectronic devices.

  View details for DOI 10.1038/s41467-020-14438-2

  View details for PubMedID 32001696

• Sub-20 nm Core-Shell-Shell Nanoparticles for Bright Upconversion and Enhanced Forster Resonant Energy Transfer. Journal of the American Chemical Society Siefe, C., Mehlenbacher, R. D., Peng, C. S., Zhang, Y., Fischer, S., Lay, A., McLellan, C. A., Alivisatos, A. P., Chu, S., Dionne, J. A. 2019

  Abstract

  Upconverting nanoparticles provide valuable benefits as optical probes for bioimaging and Forster resonant energy transfer (FRET) due to their high signal-to-noise ratio, photostability, and biocompatibility; yet, making nanoparticles small yields a significant decay in brightness due to increased surface quenching. Approaches to improve the brightness of UCNPs exist but often require increased nanoparticle size. Here we present a unique core-shell-shell nanoparticle architecture for small (sub-20 nm), bright upconversion with several key features: (1) maximal sensitizer concentration in the core for high near-infrared absorption, (2) efficient energy transfer between core and interior shell for strong emission, and (3) emitter localization near the nanoparticle surface for efficient FRET. This architecture consists of beta-NaYbF4 (core) @NaY0.8-xErxGd0.2F4 (interior shell) @NaY0.8Gd0.2F4 (exterior shell), where sensitizer and emitter ions are partitioned into core and interior shell, respectively. Emitter concentration is varied (x = 1, 2, 5, 10, 20, 50, and 80%) to investigate influence on single particle brightness, upconversion quantum yield, decay lifetimes, and FRET coupling. We compare these seven samples with the field-standard core-shell architecture of beta-NaY0.58Gd0.2Yb0.2Er0.02F4 (core) @NaY0.8Gd0.2F4 (shell), with sensitizer and emitter ions codoped in the core. At a single particle level, the core-shell-shell design was up to 2-fold brighter than the standard core-shell design. Further, by coupling a fluorescent dye to the surface of the two different architectures, we demonstrated up to 8-fold improved emission enhancement with the core-shell-shell compared to the core-shell design. We show how, given proper consideration for emitter concentration, we can design a unique nanoparticle architecture to yield comparable or improved brightness and FRET coupling within a small volume.

  View details for DOI 10.1021/jacs.9b09571

  View details for PubMedID 31592655

• Nanodiamond Integration with Photonic Devices LASER & PHOTONICS REVIEWS Rodulaski, M., Zhang, J., Tzeng, Y., Lagoudakis, K. G., Ishiwata, H., Dory, C., Fischer, K. A., Kelaita, Y. A., Sun, S., Maurer, P. C., Alassaad, K., Ferro, G., Shen, Z., Melosh, N. A., Chu, S., Vuckovic, J. 2019

  View details for DOI 10.1002/lpor.201800316

  View details for Web of Science ID 000480009200001

• A Magneto-Optical Nanoplatform for Multimodality Imaging of Tumors in Mice. ACS nano Song, G., Zheng, X., Wang, Y., Xia, X., Chu, S., Rao, J. 2019

  Abstract

  Multimodality imaging involves the use of more imaging modes to image the same living subjects and is now generally preferred in clinics for cancer imaging. Here we present multimodality-Magnetic Particle Imaging (MPI), Magnetic Resonance Imaging (MRI), Photoacoustic, Fluorescent-nanoparticles (termed MMPF NPs) for imaging tumor xenografts in living mice. MMPF NPs provide long-term (more than 2 months), dynamic, and accurate quantification, in vivo, of NPs and in real time by MPI. Moreover, MMPF NPs offer ultrasensitive MPI imaging of tumors (the tumor ROI increased by 30.6 times over that of preinjection). Moreover, the nanoparticle possessed a long-term blood circulation time (half-life at 49 h) and high tumor uptake (18% ID/g). MMPF NPs have been demonstrated for imaging breast and brain tumor xenografts in both subcutaneous and orthotopic models in mice via simultaneous MPI, MRI, fluorescence, and photoacoustic imaging with excellent tumor contrast to normal tissues.

  View details for DOI 10.1021/acsnano.9b01436

  View details for PubMedID 31244043

• Upper limit for angular compounding speckle reduction APPLIED PHYSICS LETTERS Winetraub, Y., Wu, C., Collins, G. P., Chu, S., de la Zerda, A. 2019; 114 (21)

  View details for DOI 10.1063/1.5088709

  View details for Web of Science ID 000482438000007

• Bright sub-20-nm cathodoluminescent nanoprobes for electron microscopy NATURE NANOTECHNOLOGY Prigozhin, M. B., Maurer, P. C., Courtis, A. M., Liu, N., Wisser, M. D., Siefe, C., Tian, B., Chan, E., Song, G., Fischer, S., Aloni, S., Ogletree, D., Barnard, E. S., Joubert, L., Rao, J., Alivisatos, A., Macfarlane, R. M., Cohen, B. E., Cui, Y., Dionne, J. A., Chu, S. 2019; 14 (5): 420-+

  View details for DOI 10.1038/s41565-019-0395-0

  View details for Web of Science ID 000467053100016

• Bright sub-20-nm cathodoluminescent nanoprobes for electron microscopy. Nature nanotechnology Prigozhin, M. B., Maurer, P. C., Courtis, A. M., Liu, N., Wisser, M. D., Siefe, C., Tian, B., Chan, E., Song, G., Fischer, S., Aloni, S., Ogletree, D. F., Barnard, E. S., Joubert, L., Rao, J., Alivisatos, A. P., Macfarlane, R. M., Cohen, B. E., Cui, Y., Dionne, J. A., Chu, S. 2019

  Abstract

  Electron microscopy has been instrumental in our understanding of complex biological systems. Although electron microscopy reveals cellular morphology with nanoscale resolution, it does not provide information on the location of different types of proteins. An electron-microscopy-based bioimaging technology capable of localizing individual proteins and resolving protein-protein interactions with respect to cellular ultrastructure would provide important insights into the molecular biology of a cell. Here, we synthesize small lanthanide-doped nanoparticles and measure the absolute photon emission rate of individual nanoparticles resulting from a given electron excitation flux (cathodoluminescence). Our results suggest that the optimization of nanoparticle composition, synthesis protocols and electron imaging conditions can lead to sub-20-nm nanolabels that would enable high signal-to-noise localization of individual biomolecules within a cellular context. In ensemble measurements, these labels exhibit narrow spectra of nine distinct colours, so the imaging of biomolecules in a multicolour electron microscopy modality may be possible.

  View details for PubMedID 30833691

• Breathing-Mimicking Electrocatalysis for Oxygen Evolution and Reduction JOULE Li, J., Zhu, Y., Chen, W., Lu, Z., Xu, J., Pei, A., Peng, Y., Zheng, X., Zhang, Z., Chu, S., Cui, Y. 2019; 3 (2): 557–69

  View details for DOI 10.1016/j.joule.2018.11.015

  View details for Web of Science ID 000460076100021

• Direct electrochemical generation of supercooled sulfur microdroplets well below their melting temperature. Proceedings of the National Academy of Sciences of the United States of America Liu, N., Zhou, G., Yang, A., Yu, X., Shi, F., Sun, J., Zhang, J., Liu, B., Wu, C., Tao, X., Sun, Y., Cui, Y., Chu, S. 2019

  Abstract

  Supercooled liquid sulfur microdroplets were directly generated from polysulfide electrochemical oxidation on various metal-containing electrodes. The sulfur droplets remain liquid at 155 °C below sulfur's melting point (T m = 115 °C), with fractional supercooling change (T m - T sc)/T m larger than 0.40. In operando light microscopy captured the rapid merging and shape relaxation of sulfur droplets, indicating their liquid nature. Micropatterned electrode and electrochemical current allow precise control of the location and size of supercooled microdroplets, respectively. Using this platform, we initiated and observed the rapid solidification of supercooled sulfur microdroplets upon crystalline sulfur touching, which confirms supercooled sulfur's metastability at room temperature. In addition, the formation of liquid sulfur in electrochemical cell enriches lithium-sulfur-electrolyte phase diagram and potentially may create new opportunities for high-energy Li-S batteries.

  View details for PubMedID 30602455

• Upper limit for angular compounding speckle reduction Winetraub, Y., Wu, C., Chu, S., de la Zerda, A., Fujimoto, J. G., Izatt, J. A. SPIE-INT SOC OPTICAL ENGINEERING. 2019

  View details for DOI 10.1117/12.2511428

  View details for Web of Science ID 000466475200018

• Frequency Tunable Single-Photon Emission From a Single Atomic Defect in a Solid Sun, S., Zhang, J., Fischer, K. A., Burek, M. J., Dory, C., Lagoudakis, K. G., Tzeng, Y., Radulaski, M., Kelaita, Y., Safavi-Naeini, A., Shen, Z., Melosh, N. A., Chu, S., Loncar, M., Vuckovic, J., IEEE IEEE. 2019

  View details for Web of Science ID 000482226303114

• Optimization of the Trade-Off Between Speckle Reduction and Axial Resolution in Frequency Compounding IEEE TRANSACTIONS ON MEDICAL IMAGING Li, Y., Winetraub, Y., Liba, O., de la Zerda, A., Chu, S. 2019; 38 (1): 107–12

  Abstract

  We measured the reduction of speckle by frequency compounding using Gaussian pulses, which have the least time-bandwidth product. The experimental results obtained from a tissue mimicking phantom agree quantitatively with numerical simulations of randomly distributed point scatterers. For a fixed axial resolution, the amount of speckle reduction is found to approach a maximum as the number of bands increases while the total spectral range that they cover is kept constant. An analytical solution of the maximal speckle reduction is derived and shows that the maximum improves approximately as the inverse square root of the Gaussian pulse bandwidth. Since the axial resolution is proportional to the inverse of the pulse bandwidth, an optimized trade-off between speckle reduction and axial resolution is obtained. Considerations for the applications of the optimized trade-off are discussed.

  View details for DOI 10.1109/TMI.2018.2856857

  View details for Web of Science ID 000455110500011

  View details for PubMedID 30028694

• Address harassment now SCIENCE Hamburg, M., Hockfield, S., Chu, S. 2018; 361 (6408): 1167

  View details for PubMedID 30237328

• Single upconversion nanoparticle imaging at sub-10 W cm(-2) irradiance NATURE PHOTONICS Liu, Q., Zhang, Y., Peng, C., Yang, T., Joubert, L., Chu, S. 2018; 12 (9): 548–53

  View details for DOI 10.1038/s41566-018-0217-1

  View details for Web of Science ID 000443022200014

• Single upconversion nanoparticle imaging at sub-10 W cm-2 irradiance. Nature photonics Liu, Q., Zhang, Y., Peng, C. S., Yang, T., Joubert, L. M., Chu, S. 2018; 12 (9): 548-553

  Abstract

  Lanthanide-doped upconversion nanoparticles (UCNPs) are promising single-molecule probes given their non-blinking, photobleach-resistant luminescence upon infrared excitation. However, the weak luminescence of sub-50 nm UCNPs limits their single-particle detection to above 10 kWcm-2 that is impractical for live cell imaging. Here, we systematically characterize single-particle luminescence for UCNPs with various formulations over a 106 variation in incident power, down to 8 Wcm-2. A core-shell-shell (CSS) structure (NaYF4@NaYb1-xF4:Erx@NaYF4) is shown to be significantly brighter than the commonly used NaY0.78F4:Yb0.2Er0.02. At 8 Wcm-2, the 8% Er3+ CSS particles exhibit a 150-fold enhancement given their high sensitizer Yb3+ content and the presence of an inert shell to prevent energy migration to defects. Moreover, we reveal power-dependent luminescence enhancement from the inert shell, which explains the discrepancy in enhancement factors reported by ensemble and previous single-particle measurements. These brighter probes open the possibility of cellular and single-molecule tracking at low irradiance.

  View details for DOI 10.1038/s41566-018-0217-1

  View details for PubMedID 31258619

  View details for PubMedCentralID PMC6599589

• Cavity-Enhanced Raman Emission from a Single Color Center in a Solid. Physical review letters Sun, S., Zhang, J. L., Fischer, K. A., Burek, M. J., Dory, C., Lagoudakis, K. G., Tzeng, Y., Radulaski, M., Kelaita, Y., Safavi-Naeini, A., Shen, Z., Melosh, N. A., Chu, S., Loncar, M., Vuckovic, J. 2018; 121 (8): 083601

  Abstract

  We demonstrate cavity-enhanced Raman emission from a single atomic defect in a solid. Our platform is a single silicon-vacancy center in diamond coupled with a monolithic diamond photonic crystal cavity. The cavity enables an unprecedented frequency tuning range of the Raman emission (100GHz) that significantly exceeds the spectral inhomogeneity of silicon-vacancy centers in diamond nanostructures. We also show that the cavity selectively suppresses the phonon-induced spontaneous emission that degrades the efficiency of Raman photon generation. Our results pave the way towards photon-mediated many-body interactions between solid-state quantum emitters in a nanophotonic platform.

  View details for PubMedID 30192607

• An Ultrastrong Double-Layer Nanodiamond Interface for Stable Lithium Metal Anodes JOULE Liu, Y., Tzeng, Y., Lin, D., Pei, A., Lu, H., Melosh, N. A., Shen, Z., Chu, S., Cui, Y. 2018; 2 (8): 1595–1609

  View details for DOI 10.1016/j.joule.2018.05.007

  View details for Web of Science ID 000441627400022

• Efficient electrocatalytic CO2 reduction on a three-phase interface NATURE CATALYSIS Li, J., Chen, G., Zhu, Y., Liang, Z., Pei, A., Wu, C., Wang, H., Lee, H., Liu, K., Chu, S., Cui, Y. 2018; 1 (8): 592–600

  View details for DOI 10.1038/s41929-018-0108-3

  View details for Web of Science ID 000446621900009

• Strongly Cavity-Enhanced Spontaneous Emission from Silicon-Vacancy Centers in Diamond NANO LETTERS Zhang, J., Sun, S., Burek, M. J., Dory, C., Tzeng, Y., Fischer, K. A., Kelaita, Y., Lardakis, K. G., Radulaski, M., Shen, Z., Melosh, N. A., Chu, S., Loncar, M., Vuckovic, J. 2018; 18 (2): 1360–65

  Abstract

  Quantum emitters are an integral component for a broad range of quantum technologies, including quantum communication, quantum repeaters, and linear optical quantum computation. Solid-state color centers are promising candidates for scalable quantum optics due to their long coherence time and small inhomogeneous broadening. However, once excited, color centers often decay through phonon-assisted processes, limiting the efficiency of single-photon generation and photon-mediated entanglement generation. Herein, we demonstrate strong enhancement of spontaneous emission rate of a single silicon-vacancy center in diamond embedded within a monolithic optical cavity, reaching a regime in which the excited-state lifetime is dominated by spontaneous emission into the cavity mode. We observe 10-fold lifetime reduction and 42-fold enhancement in emission intensity when the cavity is tuned into resonance with the optical transition of a single silicon-vacancy center, corresponding to 90% of the excited-state energy decay occurring through spontaneous emission into the cavity mode. We also demonstrate the largest coupling strength (g/2π = 4.9 ± 0.3 GHz) and cooperativity (C = 1.4) to date for color-center-based cavity quantum electrodynamics systems, bringing the system closer to the strong coupling regime.

  View details for DOI 10.1021/acs.nanolett.7b05075

  View details for Web of Science ID 000425559700102

  View details for PubMedID 29377701

• Strongly Cavity-Enhanced Spontaneous Emission from Silicon-Vacancy Centers in Diamond NANO LETTERS Zhang, J. L., Sun, S., Burek, M. J., Dory, C., Tzeng, Y., Fischer, K. A., Kelaita, Y., Lagoudakis, K. G., Radulaski, M., Shen, Z., Melosh, N. A., Chu, S., Lončar, M., Vučković, J. 2018; 18: 1360 -1365
• Speckle-Modulation for Speckle Reduction in Optical Coherence Tomography Liba, O., Lew, M. D., SoRelle, E. D., Dutta, R., Sen, D., Moshfeghi, D. M., Chu, S., de la Zerda, A., Izatt, J. A., Fujimoto, J. G., Tuchin, V. V. SPIE-INT SOC OPTICAL ENGINEERING. 2018

  View details for DOI 10.1117/12.2289405

  View details for Web of Science ID 000453776500010

• Atomic structure of sensitive battery materials and Interfaces revealed by cryo-electron microscopy SCIENCE Li, Y., Li, Y., Pei, A., Yan, K., Sun, Y., Wu, C., Joubert, L., Chin, R., Koh, A., Yu, Y., Perrino, J., Butz, B., Chu, S., Cui, Y. 2017; 358 (6362): 506–10

  Abstract

  Whereas standard transmission electron microscopy studies are unable to preserve the native state of chemically reactive and beam-sensitive battery materials after operation, such materials remain pristine at cryogenic conditions. It is then possible to atomically resolve individual lithium metal atoms and their interface with the solid electrolyte interphase (SEI). We observe that dendrites in carbonate-based electrolytes grow along the <111> (preferred), <110>, or <211> directions as faceted, single-crystalline nanowires. These growth directions can change at kinks with no observable crystallographic defect. Furthermore, we reveal distinct SEI nanostructures formed in different electrolytes.

  View details for PubMedID 29074771

• STEVEN CHU NATURE Chu, S. 2017; 550 (7675): S64

  View details for Web of Science ID 000412829500006

• THE REAL CLIMATE DEBATE NATURE Hodson, R., Agre, P. 2017; 550 (7675): S62

  View details for PubMedID 29019971

• Speckle-modulating optical coherence tomography in living mice and humans. Nature communications Liba, O., Lew, M. D., SoRelle, E. D., Dutta, R., Sen, D., Moshfeghi, D. M., Chu, S., de la Zerda, A. 2017; 8: 15845

  Abstract

  Optical coherence tomography (OCT) is a powerful biomedical imaging technology that relies on the coherent detection of backscattered light to image tissue morphology in vivo. As a consequence, OCT is susceptible to coherent noise (speckle noise), which imposes significant limitations on its diagnostic capabilities. Here we show speckle-modulating OCT (SM-OCT), a method based purely on light manipulation that virtually eliminates speckle noise originating from a sample. SM-OCT accomplishes this by creating and averaging an unlimited number of scans with uncorrelated speckle patterns without compromising spatial resolution. Using SM-OCT, we reveal small structures in the tissues of living animals, such as the inner stromal structure of a live mouse cornea, the fine structures inside the mouse pinna, and sweat ducts and Meissner's corpuscle in the human fingertip skin-features that are otherwise obscured by speckle noise when using conventional OCT or OCT with current state of the art speckle reduction methods.

  View details for DOI 10.1038/ncomms15845

  View details for PubMedID 28632205

  View details for PubMedCentralID PMC5481831

• A half-wave rectified alternating current electrochemical method for uranium extraction from seawater NATURE ENERGY Liu, C., Hsu, P., Xie, J., Zhao, J., Wu, T., Wang, H., Liu, W., Zhang, J., Chu, S., Cui, Y. 2017; 2 (4)

  View details for DOI 10.1038/nenergy.2017.7

  View details for Web of Science ID 000402829300023

• Vertical-Substrate MPCVD Epitaxial Nanodiamond Growth. Nano letters Tzeng, Y., Zhang, J. L., Lu, H., Ishiwata, H., Dahl, J., Carlson, R. M., Yan, H., Schreiner, P. R., Vuckovic, J., Shen, Z., Melosh, N., Chu, S. 2017

  Abstract

  Color center-containing nanodiamonds have many applications in quantum technologies and biology. Diamondoids, molecular-sized diamonds have been used as seeds in chemical vapor deposition (CVD) growth. However, optimizing growth conditions to produce high crystal quality nanodiamonds with color centers requires varying growth conditions that often leads to ad-hoc and time-consuming, one-at-a-time testing of reaction conditions. In order to rapidly explore parameter space, we developed a microwave plasma CVD technique using a vertical, rather than horizontally oriented stage-substrate geometry. With this configuration, temperature, plasma density, and atomic hydrogen density vary continuously along the vertical axis of the substrate. This variation allowed rapid identification of growth parameters that yield single crystal diamonds down to 10 nm in size and 75 nm diameter optically active center silicon-vacancy (Si-V) nanoparticles. Furthermore, this method may provide a means of incorporating a wide variety of dopants in nanodiamonds without ion irradiation damage.

  View details for DOI 10.1021/acs.nanolett.6b04543

  View details for PubMedID 28182433

• The path towards sustainable energy NATURE MATERIALS Chu, S., Cui, Y., Liu, N. 2017; 16 (1): 16-22

  Abstract

  Civilization continues to be transformed by our ability to harness energy beyond human and animal power. A series of industrial and agricultural revolutions have allowed an increasing fraction of the world population to heat and light their homes, fertilize and irrigate their crops, connect to one another and travel around the world. All of this progress is fuelled by our ability to find, extract and use energy with ever increasing dexterity. Research in materials science is contributing to progress towards a sustainable future based on clean energy generation, transmission and distribution, the storage of electrical and chemical energy, energy efficiency, and better energy management systems.

  View details for DOI 10.1038/nmat4834

  View details for Web of Science ID 000391343300010

• Complete coherent control of silicon vacancies in diamond nanopillars containing single defect centers OPTICA Zhang, J. L., Lagoudakis, K. G., Tzeng, Y., Dory, C., Radulaski, M., Kelaita, Y., Fischer, K. A., Sun, S., Shen, Z., Melosh, N., Chu, S., Vuckovic, J. 2017; 4 (11): 1317-1321

  View details for DOI 10.1364/OPTICA.4.001317

• Complete Coherent Control of Silicon-Vacancies in Diamond Nanopillars Containing Single Defect Centers Zhang, J., Lagoudakis, K. G., Tzeng, Y., Dory, C., Radulaski, M., Kelaita, Y., Fischer, K. A., Shen, Z., Melosh, N. A., Chu, S., Vuckovic, J., IEEE IEEE. 2017

  View details for Web of Science ID 000427296200411

• Atomic structure of sensitive battery materials and interfaces revealed by cryo–electron microscopy SCIENCE Li, Y., Li, Y., Pei, A., Yan, K., Sun, Y., Wu, C., Joubert, L. M., Chin, R., Koh, A. L., Yu, Y., Perrino, J., Butz, B., Chu, S., Cui, Y. 2017; 358: 506–510
• Complete Coherent Control of Silicon-Vacancies in Diamond Nanopillars Containing Single Defect Centers OPTICA Zhang, J. L., Lagoudakis, K. G., Tzeng, Y., Dory, C., Radulaski, M., Kelaita, Y., Fischer, K. A., Shen, Z., Melosh, N. A., Chu, S., Vučković, J. 2017; 4: 1317-1321
• A half-wave rectified alternating current electrochemical method for uranium extraction from seawater NATURE ENERGY Liu, C., Hsu, P., Xie, J., Zhao, J., Wu, T., Wang, H., Liu, W., Zhang, J., Chu, S., Cui, Y. 2017; 2: 17007
• Speckle-modulating optical coherence tomography in living mice and humans NATURE COMMUNICATIONS Liba, O., Lew, M. D., SoRelle, E. D., Dutta, R., Sen, D., Moshfeghi, D. M., Chu, S., de la Zerda, A. 2017; 8: 15845

  Abstract

  Optical coherence tomography (OCT) is a powerful biomedical imaging technology that relies on the coherent detection of backscattered light to image tissue morphology in vivo. As a consequence, OCT is susceptible to coherent noise (speckle noise), which imposes significant limitations on its diagnostic capabilities. Here we show speckle-modulating OCT (SM-OCT), a method based purely on light manipulation that virtually eliminates speckle noise originating from a sample. SM-OCT accomplishes this by creating and averaging an unlimited number of scans with uncorrelated speckle patterns without compromising spatial resolution. Using SM-OCT, we reveal small structures in the tissues of living animals, such as the inner stromal structure of a live mouse cornea, the fine structures inside the mouse pinna, and sweat ducts and Meissner's corpuscle in the human fingertip skin-features that are otherwise obscured by speckle noise when using conventional OCT or OCT with current state of the art speckle reduction methods.

  View details for DOI 10.1038/ncomms15845

  View details for PubMedCentralID PMC5481831

• The path towards sustainable energy. Nature materials Chu, S., Cui, Y., Liu, N. 2016; 16 (1): 16-22

  Abstract

  Civilization continues to be transformed by our ability to harness energy beyond human and animal power. A series of industrial and agricultural revolutions have allowed an increasing fraction of the world population to heat and light their homes, fertilize and irrigate their crops, connect to one another and travel around the world. All of this progress is fuelled by our ability to find, extract and use energy with ever increasing dexterity. Research in materials science is contributing to progress towards a sustainable future based on clean energy generation, transmission and distribution, the storage of electrical and chemical energy, energy efficiency, and better energy management systems.

  View details for DOI 10.1038/nmat4834

  View details for PubMedID 27994253

• High-Performance Lithium Metal Negative Electrode with a Soft and Flowable Polymer Coating ACS ENERGY LETTERS Zheng, G., Wang, C., Pei, A., Lopez, J., Shi, F., Chen, Z., Sendek, A. D., Lee, H., Lu, Z., Schneider, H., Safont-Sempere, M. M., Chu, S., Bao, Z., Cui, Y. 2016; 1 (6): 1247-1255

  View details for DOI 10.1021/acsenergylett.6b00456

  View details for Web of Science ID 000390086400028

• Sr Betavoltaic Power Source. Scientific reports Dixon, J., Rajan, A., Bohlemann, S., Coso, D., Upadhyaya, A. D., Rohatgi, A., Chu, S., Majumdar, A., Yee, S. 2016; 6: 38182-?

  Abstract

  Betavoltaic energy converters (i.e., β-batteries) are attractive power sources because of their potential for high energy densities (>200 MWh/kg) and long duration continuous discharge (>1 year). However, conversion efficiencies have been historically low (<3%). High efficiency devices can be achieved by matching β-radiation transport length scales with the device physics length scales. In this work, the efficiency of c-Si devices using high-energy (>1 MeV) electrons emitted from (90)Sr as a power source is investigated. We propose a design for a >10% efficient betavoltaic device, which generates 1 W of power. A Varian Clinac iX is used to simulate the high-energy electrons emitted from (90)Sr, and a high efficiency c-Si photovoltaic cell is used as the converter. The measured conversion efficiency is 16%. This relatively high value is attributed to proper length scale matching and the generation of secondary electrons in c-Si by the primary β-particles.

  View details for DOI 10.1038/srep38182

  View details for PubMedID 27905521

  View details for PubMedCentralID PMC5131278

• Evaluation of a Silicon Sr-90 Betavoltaic Power Source SCIENTIFIC REPORTS Dixon, J., Rajan, A., Bohlemann, S., Coso, D., Upadhyaya, A. D., Rohatgi, A., Chu, S., Majumdar, A., Yee, S. 2016; 6

  Abstract

  Betavoltaic energy converters (i.e., β-batteries) are attractive power sources because of their potential for high energy densities (>200 MWh/kg) and long duration continuous discharge (>1 year). However, conversion efficiencies have been historically low (<3%). High efficiency devices can be achieved by matching β-radiation transport length scales with the device physics length scales. In this work, the efficiency of c-Si devices using high-energy (>1 MeV) electrons emitted from (90)Sr as a power source is investigated. We propose a design for a >10% efficient betavoltaic device, which generates 1 W of power. A Varian Clinac iX is used to simulate the high-energy electrons emitted from (90)Sr, and a high efficiency c-Si photovoltaic cell is used as the converter. The measured conversion efficiency is 16%. This relatively high value is attributed to proper length scale matching and the generation of secondary electrons in c-Si by the primary β-particles.

  View details for DOI 10.1038/srep38182

  View details for Web of Science ID 000388995400001

  View details for PubMedCentralID PMC5131278

• Super-resolution molecular imaging with photostable nanoprobes Prigozhin, M., Maurer, P., Courtis, A., Zheng, X., Liu, N., Collins, J., Aloni, S., Ogletree, F., Macfarlane, R., Cui, Y., Rao, J., Alivisatos, P., Chu, S. AMER CHEMICAL SOC. 2016

  View details for Web of Science ID 000431460402662

• Wafer-Size and Single-Crystal MoSe2 Atomically Thin Films Grown on GaN Substrate for Light Emission and Harvesting ACS APPLIED MATERIALS & INTERFACES Chen, Z., Liu, H., Chen, X., Chu, G., Chu, S., Zhang, H. 2016; 8 (31): 20267-20273

  Abstract

  Two-dimensional (2D) atomic-layered semiconductors are important for next-generation electronics and optoelectronics. Here, we designed the growth of an MoSe2 atomic layer on a lattice-matched GaN semiconductor substrate. The results demonstrated that the MoSe2 films were less than three atomic layers thick and were single crystalline of MoSe2 over the entire GaN substrate. The ultrathin MoSe2/GaN heterojunction diode demonstrated ∼850 nm light emission and could also be used in photovoltaic applications.

  View details for DOI 10.1021/acsami.6b04768

  View details for Web of Science ID 000381331600050

  View details for PubMedID 27409977

• Enhancing Quantum Yield via Local Symmetry Distortion in Lanthanide-Based Upconverting Nanoparticles ACS PHOTONICS Wisser, M. D., Fischer, S., Maurer, P. C., Bronstein, N. D., Chu, S., Alivisatos, A. P., Salleo, A., Dionne, J. A. 2016; 3 (8): 1523-1530

  View details for DOI 10.1021/acsphotonics.6b00166

  View details for Web of Science ID 000381717600023

• Nanofiber Air Filters with High-Temperature Stability for Efficient PM2.5 Removal from the Pollution Sources NANO LETTERS Zhang, R., Liu, C., Hsu, P., Zhang, C., Liu, N., Zhang, J., Lee, H. R., Lu, Y., Qiu, Y., Chu, S., Cui, Y. 2016; 16 (6): 3642-3649

  Abstract

  Here, we developed high-efficiency (>99.5%) polyimide-nanofiber air filters for the high temperature PM2.5 removal. The polyimide nanofibers exhibited high thermal stability, and the PM2.5 removal efficiency was kept unchanged when temperature ranged from 25-370 °C. These filters had high air flux with very low pressure drop. They could continuously work for >120 h for PM2.5 index >300. A field-test showed that they could effectively remove >99.5% PM particles from car exhaust at high temperature.

  View details for DOI 10.1021/acs.nanolett.6b00771

  View details for Web of Science ID 000377642700034

  View details for PubMedID 27167892

• Selective deposition and stable encapsulation of lithium through heterogeneous seeded growth NATURE ENERGY Yan, K., Lu, Z., Lee, H., Xiong, F., Hsu, P., Li, Y., Zhao, J., Chu, S., Cui, Y. 2016; 1

  View details for DOI 10.1038/NENERGY.2016.10

  View details for Web of Science ID 000394104100001

• Super-Resolution Molecular Imaging with Photostable Nanoprobes Prigozhin, M. B., Maurer, P. C., Liu, N., Courtis, A. M., Aloni, S., Ogletree, F. D., MacFarlane, R. M., Cui, Y., Alivisatos, P. A., Chu, S. CELL PRESS. 2016: 161A

  View details for DOI 10.1016/j.bpj.2015.11.901

  View details for Web of Science ID 000375093800293

• Shelterin Protects Chromosome Ends by Compacting Telomeric Chromatin CELL Bandaria, J. N., Qin, P., Berk, V., Chu, S., Yildiz, A. 2016; 164 (4): 735-746

  Abstract

  Telomeres, repetitive DNA sequences at chromosome ends, are shielded against the DNA damage response (DDR) by the shelterin complex. To understand how shelterin protects telomere ends, we investigated the structural organization of telomeric chromatin in human cells using super-resolution microscopy. We found that telomeres form compact globular structures through a complex network of interactions between shelterin subunits and telomeric DNA, but not by DNA methylation, histone deacetylation, or histone trimethylation at telomeres and subtelomeric regions. Mutations that abrogate shelterin assembly or removal of individual subunits from telomeres cause up to a 10-fold increase in telomere volume. Decompacted telomeres accumulate DDR signals and become more accessible to telomere-associated proteins. Recompaction of telomeric chromatin using an orthogonal method displaces DDR signals from telomeres. These results reveal the chromatin remodeling activity of shelterin and demonstrate that shelterin-mediated compaction of telomeric chromatin provides robust protection of chromosome ends against the DDR machinery.

  View details for DOI 10.1016/j.cell.2016.01.036

  View details for Web of Science ID 000369998300018

  View details for PubMedID 26871633

  View details for PubMedCentralID PMC4762449

• DOI: 10.1038/srep38182 Evaluation of a Silicon 90Sr Betavoltaic Power Source Dixon, J., et al 2016; 6
• Emitter-Cavity Coupling in Hybrid Silicon Carbide-Nanodiamond Microdisk Resonators Radulaski, M., Tzeng, Y., Zhang, J., Ishiwata, H., Lagoudakis, K. G., Souliere, V., Ferro, G., Shen, Z., Melosh, N. A., Chu, S., Vuckovic, J., IEEE IEEE. 2016

  View details for Web of Science ID 000391286402328

• THE NAI FELLOW PROFILE: AN INTERVIEW WITH DR. STEVEN CHU TECHNOLOGY AND INNOVATION Chu, S., Macuare, K. A. 2016; 17 (4): 187–92

  View details for DOI 10.3727/194982416X14520374943022

  View details for Web of Science ID 000447554100007

• Powernet for Distributed Energy Resource Networks Radovanovic, A., Ramesh, A., Koningstein, R., Fork, D., Weber, W., Kim, S., Schmalzried, J., Sastry, J., Dikovsky, M., Bozhkov, K., Pinheiro, E., Lebsack, C., Collyer, S., Somani, A., Rajagopal, R., Majumdar, A., Qin, J., Cezar, G., Rivas, J., El Gamal, A., Gruenich, D., Chu, S., Kiliccote, S., IEEE IEEE. 2016

  View details for Web of Science ID 000399937903196

• Ras-GTP dimers activate the Mitogen-Activated Protein Kinase (MAPK) pathway PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Nan, X., Tamgueney, T. M., Collisson, E. A., Lin, L., Pitt, C., Galeas, J., Lewis, S., Gray, J. W., McCormick, F., Chu, S. 2015; 112 (26): 7996-8001

  Abstract

  Rat sarcoma (Ras) GTPases regulate cell proliferation and survival through effector pathways including Raf-MAPK, and are the most frequently mutated genes in human cancer. Although it is well established that Ras activity requires binding to both GTP and the membrane, details of how Ras operates on the cell membrane to activate its effectors remain elusive. Efforts to target mutant Ras in human cancers to therapeutic benefit have also been largely unsuccessful. Here we show that Ras-GTP forms dimers to activate MAPK. We used quantitative photoactivated localization microscopy (PALM) to analyze the nanoscale spatial organization of PAmCherry1-tagged KRas 4B (hereafter referred to KRas) on the cell membrane under various signaling conditions. We found that at endogenous expression levels KRas forms dimers, and KRas(G12D), a mutant that constitutively binds GTP, activates MAPK. Overexpression of KRas leads to formation of higher order Ras nanoclusters. Conversely, at lower expression levels, KRas(G12D) is monomeric and activates MAPK only when artificially dimerized. Moreover, dimerization and signaling of KRas are both dependent on an intact CAAX (C, cysteine; A, aliphatic; X, any amino acid) motif that is also known to mediate membrane localization. These results reveal a new, dimerization-dependent signaling mechanism of Ras, and suggest Ras dimers as a potential therapeutic target in mutant Ras-driven tumors.

  View details for DOI 10.1073/pnas.1509123112

  View details for PubMedID 26080442

• Polymer Nanofiber-Guided Uniform Lithium Deposition for Battery Electrodes NANO LETTERS Liang, Z., Zheng, G., Liu, C., Liu, N., Li, W., Yan, K., Yao, H., Hsu, P., Chu, S., Cui, Y. 2015; 15 (5): 2910-2916

  Abstract

  Lithium metal is one of the most promising candidates as an anode material for next-generation energy storage systems due to its highest specific capacity (3860 mAh/g) and lowest redox potential of all. The uncontrolled lithium dendrite growth that causes a poor cycling performance and serious safety hazards, however, presents a significant challenge for the realization of lithium metal-based batteries. Here, we demonstrate a novel electrode design by placing a three-dimensional (3D) oxidized polyacrylonitrile nanofiber network on top of the current collector. The polymer fiber with polar surface functional groups could guide the lithium ions to form uniform lithium metal deposits confined on the polymer fiber surface and in the 3D polymer layer. We showed stable cycling of lithium metal anode with an average Coulombic efficiency of 97.4% over 120 cycles in ether-based electrolyte at a current density of 3 mA/cm(2) for a total of 1 mAh/cm(2) of lithium.

  View details for DOI 10.1021/nl5046318

  View details for Web of Science ID 000354906000021

  View details for PubMedID 25822282

• Microscopy 2.0 Chu, S., IEEE IEEE. 2015

  View details for Web of Science ID 000370627101142

• Artificial Graphene and Related Photonic Lattices Generated With a Simple Method IEEE PHOTONICS JOURNAL Gao, Y., Song, D., Chu, S., Chen, Z. 2014; 6 (6)

  View details for DOI 10.1109/JPHOT.2014.2363436

  View details for Web of Science ID 000345576700016

• Ultrathin two-dimensional atomic crystals as stable interfacial layer for improvement of lithium metal anode. Nano letters Yan, K., Lee, H., Gao, T., Zheng, G., Yao, H., Wang, H., Lu, Z., Zhou, Y., Liang, Z., Liu, Z., Chu, S., Cui, Y. 2014; 14 (10): 6016-6022

  Abstract

  Stable cycling of lithium metal anode is challenging due to the dendritic lithium formation and high chemical reactivity of lithium with electrolyte and nearly all the materials. Here, we demonstrate a promising novel electrode design by growing two-dimensional (2D) atomic crystal layers including hexagonal boron nitride (h-BN) and graphene directly on Cu metal current collectors. Lithium ions were able to penetrate through the point and line defects of the 2D layers during the electrochemical deposition, leading to sandwiched lithium metal between ultrathin 2D layers and Cu. The 2D layers afford an excellent interfacial protection of Li metal due to their remarkable chemical stability as well as mechanical strength and flexibility, resulting from the strong intralayer bonds and ultrathin thickness. Smooth Li metal deposition without dendritic and mossy Li formation was realized. We showed stable cycling over 50 cycles with Coulombic efficiency ∼97% in organic carbonate electrolyte with current density and areal capacity up to the practical value of 2.0 mA/cm(2)and 5.0 mAh/cm(2), respectively, which is a significant improvement over the unprotected electrodes in the same electrolyte.

  View details for DOI 10.1021/nl503125u

  View details for PubMedID 25166749

• Ultrathin Two-Dimensional Atomic Crystals as Stable Interfacial Layer for Improvement of Lithium Metal Anode NANO LETTERS Yan, K., Lee, H., Gao, T., Zheng, G., Yao, H., Wang, H., Lu, Z., Zhou, Y., Liang, Z., Liu, Z., Chu, S., Cui, Y. 2014; 14 (10): 6016-6022

  Abstract

  Stable cycling of lithium metal anode is challenging due to the dendritic lithium formation and high chemical reactivity of lithium with electrolyte and nearly all the materials. Here, we demonstrate a promising novel electrode design by growing two-dimensional (2D) atomic crystal layers including hexagonal boron nitride (h-BN) and graphene directly on Cu metal current collectors. Lithium ions were able to penetrate through the point and line defects of the 2D layers during the electrochemical deposition, leading to sandwiched lithium metal between ultrathin 2D layers and Cu. The 2D layers afford an excellent interfacial protection of Li metal due to their remarkable chemical stability as well as mechanical strength and flexibility, resulting from the strong intralayer bonds and ultrathin thickness. Smooth Li metal deposition without dendritic and mossy Li formation was realized. We showed stable cycling over 50 cycles with Coulombic efficiency ∼97% in organic carbonate electrolyte with current density and areal capacity up to the practical value of 2.0 mA/cm(2)and 5.0 mAh/cm(2), respectively, which is a significant improvement over the unprotected electrodes in the same electrolyte.

  View details for DOI 10.1021/nl503125u

  View details for Web of Science ID 000343016400082

• Interconnected hollow carbon nanospheres for stable lithium metal anodes. Nature nanotechnology Zheng, G., Lee, S. W., Liang, Z., Lee, H., Yan, K., Yao, H., Wang, H., Li, W., Chu, S., Cui, Y. 2014; 9 (8): 618-623

  Abstract

  For future applications in portable electronics, electric vehicles and grid storage, batteries with higher energy storage density than existing lithium ion batteries need to be developed. Recent efforts in this direction have focused on high-capacity electrode materials such as lithium metal, silicon and tin as anodes, and sulphur and oxygen as cathodes. Lithium metal would be the optimal choice as an anode material, because it has the highest specific capacity (3,860 mAh g(-1)) and the lowest anode potential of all. However, the lithium anode forms dendritic and mossy metal deposits, leading to serious safety concerns and low Coulombic efficiency during charge/discharge cycles. Although advanced characterization techniques have helped shed light on the lithium growth process, effective strategies to improve lithium metal anode cycling remain elusive. Here, we show that coating the lithium metal anode with a monolayer of interconnected amorphous hollow carbon nanospheres helps isolate the lithium metal depositions and facilitates the formation of a stable solid electrolyte interphase. We show that lithium dendrites do not form up to a practical current density of 1 mA cm(-2). The Coulombic efficiency improves to ∼99% for more than 150 cycles. This is significantly better than the bare unmodified samples, which usually show rapid Coulombic efficiency decay in fewer than 100 cycles. Our results indicate that nanoscale interfacial engineering could be a promising strategy to tackle the intrinsic problems of lithium metal anodes.

  View details for DOI 10.1038/nnano.2014.152

  View details for PubMedID 25064396

• In vitro and in vivo radiosensitization of human glioma U251 cells induced by upregulated expression of SLC22A18 CANCER GENE THERAPY Chu, S., Zhou, Z., Karri, S., Li, Z., Zhao, J. 2014; 21 (3): 103-109

  Abstract

  Our previous study showed that solute carrier family 22 (organic cation transporter) member 18 (SLC22A18) downregulation via promoter methylation was associated with the development and progression of glioma, and the elevated expression of SLC22A18 was found to increase the sensitivity of glioma U251 cells to the anticancer drug 1,3-bis(2-chloroethyl)-1-nitrosourea. In this study, we investigated the possible upregulated expression of SLC22A18-induced enhancement of radiosensitivity of human glioma U251 cells in order to provide evidence in support of further clinical investigations. Stably overexpressing SLC22A18 human glioma U251 cells were generated to investigate the effect of SLC22A18 on the sensitivity of cells to irradiation in vitro using clonogenic survival assay. The apoptosis of U251 cells was examined with terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay. DNA damage and repair were measured using γH2AX foci. The effect of SLC22A18 on the in vivo tumor radiosensitivity was investigated in the orthotopic mice model. Upregulated expression of SLC22A18 enhanced the radiosensitivity of glioma U251 cells and also enhanced irradiation-induced apoptosis of U251 cells, but irradiation-induced apoptosis did not correlate with radiosensitizing effect of upregulated expression of SLC22A18. The repair of irradiation-induced double-strand-breaks was retarded in stably overexpressing SLC22A18 U251 cells. In the orthotopic mice model, the upregulated expression of SLC22A18 in U251 cells enhanced the effect of irradiation treatment and increased the survival time of mice. These results show that upregulated expression of SLC22A18 radiosensitizes human glioma U251 cells by suppressing DNA repair capacity.

  View details for DOI 10.1038/cgt.2014.4

  View details for Web of Science ID 000333069600003

  View details for PubMedID 24481489

• Super-Resolution Imaging of Telomeres Reveals that Compaction of Telomeric DNA by Shelterin Protects Chromosome Terminii Bandaria, J. N., Berk, V., Chu, S., Yildiz, A. CELL PRESS. 2014: 435A

  View details for DOI 10.1016/j.bpj.2013.11.2452

  View details for Web of Science ID 000337000402437

• Single-molecule superresolution imaging allows quantitative analysis of RAF multimer formation and signaling PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Nan, X., Collisson, E. A., Lewis, S., Huang, J., Tamgueney, T. M., Liphardt, J. T., McCormick, F., Gray, J. W., Chu, S. 2013; 110 (46): 18519-18524

  Abstract

  The RAF serine/threonine kinases regulate cell growth through the MAPK pathway, and are targeted by small-molecule RAF inhibitors (RAFis) in human cancer. It is now apparent that protein multimers play an important role in RAF activation and tumor response to RAFis. However, the exact stoichiometry and cellular location of these multimers remain unclear because of the lack of technologies to visualize them. In the present work, we demonstrate that photoactivated localization microscopy (PALM), in combination with quantitative spatial analysis, provides sufficient resolution to directly visualize protein multimers in cells. Quantitative PALM imaging showed that CRAF exists predominantly as cytoplasmic monomers under resting conditions but forms dimers as well as trimers and tetramers at the cell membrane in the presence of active RAS. In contrast, N-terminal truncated CRAF (CatC) lacking autoinhibitory domains forms constitutive dimers and occasional tetramers in the cytoplasm, whereas a CatC mutant with a disrupted CRAF-CRAF dimer interface does not. Finally, artificially forcing CRAF to the membrane by fusion to a RAS CAAX motif induces multimer formation but activates RAF/MAPK only if the dimer interface is intact. Together, these quantitative results directly confirm the existence of RAF dimers and potentially higher-order multimers and their involvement in cell signaling, and showed that RAF multimer formation can result from multiple mechanisms and is a critical but not sufficient step for RAF activation.

  View details for DOI 10.1073/pnas.1318188110

  View details for Web of Science ID 000326830900054

  View details for PubMedID 24158481

  View details for PubMedCentralID PMC3831949

• Ultrahigh-resolution imaging reveals formation of neuronal SNARE/Munc18 complexes in situ. Proceedings of the National Academy of Sciences of the United States of America Pertsinidis, A., Mukherjee, K., Sharma, M., Pang, Z. P., Park, S. R., Zhang, Y., Brunger, A. T., Südhof, T. C., Chu, S. 2013; 110 (30): E2812-20

  Abstract

  Membrane fusion is mediated by complexes formed by SNAP-receptor (SNARE) and Secretory 1 (Sec1)/mammalian uncoordinated-18 (Munc18)-like (SM) proteins, but it is unclear when and how these complexes assemble. Here we describe an improved two-color fluorescence nanoscopy technique that can achieve effective resolutions of up to 7.5-nm full width at half maximum (3.2-nm localization precision), limited only by stochastic photon emission from single molecules. We use this technique to dissect the spatial relationships between the neuronal SM protein Munc18-1 and SNARE proteins syntaxin-1 and SNAP-25 (25 kDa synaptosome-associated protein). Strikingly, we observed nanoscale clusters consisting of syntaxin-1 and SNAP-25 that contained associated Munc18-1. Rescue experiments with syntaxin-1 mutants revealed that Munc18-1 recruitment to the plasma membrane depends on the Munc18-1 binding to the N-terminal peptide of syntaxin-1. Our results suggest that in a primary neuron, SNARE/SM protein complexes containing syntaxin-1, SNAP-25, and Munc18-1 are preassembled in microdomains on the presynaptic plasma membrane. Our superresolution imaging method provides a framework for investigating interactions between the synaptic vesicle fusion machinery and other subcellular systems in situ.

  View details for DOI 10.1073/pnas.1310654110

  View details for PubMedID 23821748

• Ultrahigh-resolution imaging reveals formation of neuronal SNARE/Munc18 complexes in situ PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Pertsinidis, A., Mukherjee, K., Sharma, M., Pang, Z. P., Park, S. R., Zhang, Y., Brunger, A. T., Suedhof, T. C., Chu, S. 2013; 110 (30): E2812-E2820

  Abstract

  Membrane fusion is mediated by complexes formed by SNAP-receptor (SNARE) and Secretory 1 (Sec1)/mammalian uncoordinated-18 (Munc18)-like (SM) proteins, but it is unclear when and how these complexes assemble. Here we describe an improved two-color fluorescence nanoscopy technique that can achieve effective resolutions of up to 7.5-nm full width at half maximum (3.2-nm localization precision), limited only by stochastic photon emission from single molecules. We use this technique to dissect the spatial relationships between the neuronal SM protein Munc18-1 and SNARE proteins syntaxin-1 and SNAP-25 (25 kDa synaptosome-associated protein). Strikingly, we observed nanoscale clusters consisting of syntaxin-1 and SNAP-25 that contained associated Munc18-1. Rescue experiments with syntaxin-1 mutants revealed that Munc18-1 recruitment to the plasma membrane depends on the Munc18-1 binding to the N-terminal peptide of syntaxin-1. Our results suggest that in a primary neuron, SNARE/SM protein complexes containing syntaxin-1, SNAP-25, and Munc18-1 are preassembled in microdomains on the presynaptic plasma membrane. Our superresolution imaging method provides a framework for investigating interactions between the synaptic vesicle fusion machinery and other subcellular systems in situ.

  View details for DOI 10.1073/pnas.1310654110

  View details for Web of Science ID 000322112300011

  View details for PubMedID 23821748

• Studying calcium-triggered vesicle fusion in a single vesicle-vesicle content and lipid-mixing system. Nature protocols Kyoung, M., Zhang, Y., Diao, J., Chu, S., Brunger, A. T. 2013; 8 (1): 1-16

  Abstract

  This protocol describes a single vesicle-vesicle microscopy system to study Ca(2+)-triggered vesicle fusion. Donor vesicles contain reconstituted synaptobrevin and synaptotagmin-1. Acceptor vesicles contain reconstituted syntaxin and synaptosomal-associated protein 25 (SNAP-25), and they are tethered to a PEG-coated glass surface. Donor vesicles are mixed with the tethered acceptor vesicles and incubated for several minutes at a zero-Ca(2+) concentration, resulting in a collection of single interacting vesicle pairs. The donor vesicles also contain two spectrally distinct fluorophores that allow simultaneous monitoring of temporal changes of the content and membrane. Upon Ca(2+) injection into the sample chamber, our system therefore differentiates between hemifusion and complete fusion of interacting vesicle pairs and determines the temporal sequence of these events on a sub-100-millisecond time scale. Other factors such as complexin can be easily added. Our system is unique in that it monitors both content and lipid mixing and starts from a metastable state of interacting vesicle pairs before Ca(2+) injection.

  View details for DOI 10.1038/nprot.2012.134

  View details for PubMedID 23222454

  View details for PubMedCentralID PMC3566647

• Studying calcium-triggered vesicle fusion in a single vesicle-vesicle content and lipid-mixing system NATURE PROTOCOLS Kyoung, M., Zhang, Y., Diao, J., Chu, S., Brunger, A. T. 2013; 8 (1): 1-16

  Abstract

  This protocol describes a single vesicle-vesicle microscopy system to study Ca(2+)-triggered vesicle fusion. Donor vesicles contain reconstituted synaptobrevin and synaptotagmin-1. Acceptor vesicles contain reconstituted syntaxin and synaptosomal-associated protein 25 (SNAP-25), and they are tethered to a PEG-coated glass surface. Donor vesicles are mixed with the tethered acceptor vesicles and incubated for several minutes at a zero-Ca(2+) concentration, resulting in a collection of single interacting vesicle pairs. The donor vesicles also contain two spectrally distinct fluorophores that allow simultaneous monitoring of temporal changes of the content and membrane. Upon Ca(2+) injection into the sample chamber, our system therefore differentiates between hemifusion and complete fusion of interacting vesicle pairs and determines the temporal sequence of these events on a sub-100-millisecond time scale. Other factors such as complexin can be easily added. Our system is unique in that it monitors both content and lipid mixing and starts from a metastable state of interacting vesicle pairs before Ca(2+) injection.

  View details for DOI 10.1038/nprot.2012.134

  View details for Web of Science ID 000313051300001

  View details for PubMedID 23222454

  View details for PubMedCentralID PMC3566647

• Synaptic proteins promote calcium-triggered fast transition from point contact to full fusion ELIFE Diao, J., Grob, P., Cipriano, D. J., Kyoung, M., Zhang, Y., Shah, S., Amie Nguyen, A., Padolina, M., Srivastava, A., Vrljic, M., Shah, A., Nogales, E., Chu, S., Brunger, A. T. 2012; 1

  Abstract

  The molecular underpinnings of synaptic vesicle fusion for fast neurotransmitter release are still unclear. Here, we used a single vesicle-vesicle system with reconstituted SNARE and synaptotagmin-1 proteoliposomes to decipher the temporal sequence of membrane states upon Ca(2+)-injection at 250-500 μM on a 100-ms timescale. Furthermore, detailed membrane morphologies were imaged with cryo-electron microscopy before and after Ca(2+)-injection. We discovered a heterogeneous network of immediate and delayed fusion pathways. Remarkably, all instances of Ca(2+)-triggered immediate fusion started from a membrane-membrane point-contact and proceeded to complete fusion without discernible hemifusion intermediates. In contrast, pathways that involved a stable hemifusion diaphragm only resulted in fusion after many seconds, if at all. When complexin was included, the Ca(2+)-triggered fusion network shifted towards the immediate pathway, effectively synchronizing fusion, especially at lower Ca(2+)-concentration. Synaptic proteins may have evolved to select this immediate pathway out of a heterogeneous network of possible membrane fusion pathways.DOI:http://dx.doi.org/10.7554/eLife.00109.001.

  View details for DOI 10.7554/eLife.00109

  View details for Web of Science ID 000328584600005

  View details for PubMedCentralID PMC3514886

• Opportunities and challenges for a sustainable energy future NATURE Chu, S., Majumdar, A. 2012; 488 (7411): 294-303

  Abstract

  Access to clean, affordable and reliable energy has been a cornerstone of the world's increasing prosperity and economic growth since the beginning of the industrial revolution. Our use of energy in the twenty-first century must also be sustainable. Solar and water-based energy generation, and engineering of microbes to produce biofuels are a few examples of the alternatives. This Perspective puts these opportunities into a larger context by relating them to a number of aspects in the transportation and electricity generation sectors. It also provides a snapshot of the current energy landscape and discusses several research and development opportunities and pathways that could lead to a prosperous, sustainable and secure energy future for the world.

  View details for DOI 10.1038/nature11475

  View details for Web of Science ID 000307501000028

  View details for PubMedID 22895334

• Transcription initiation by human RNA polymerase II visualized at single-molecule resolution GENES & DEVELOPMENT Revyakin, A., Zhang, Z., Coleman, R. A., Li, Y., Inouye, C., Lucas, J. K., Park, S., Chu, S., Tjian, R. 2012; 26 (15): 1691-1702

  Abstract

  Forty years of classical biochemical analysis have identified the molecular players involved in initiation of transcription by eukaryotic RNA polymerase II (Pol II) and largely assigned their functions. However, a dynamic picture of Pol II transcription initiation and an understanding of the mechanisms of its regulation have remained elusive due in part to inherent limitations of conventional ensemble biochemistry. Here we have begun to dissect promoter-specific transcription initiation directed by a reconstituted human Pol II system at single-molecule resolution using fluorescence video-microscopy. We detected several stochastic rounds of human Pol II transcription from individual DNA templates, observed attenuation of transcription by promoter mutations, observed enhancement of transcription by activator Sp1, and correlated the transcription signals with real-time interactions of holo-TFIID molecules at individual DNA templates. This integrated single-molecule methodology should be applicable to studying other complex biological processes.

  View details for DOI 10.1101/gad.194936.112

  View details for Web of Science ID 000307160000007

  View details for PubMedID 22810624

• Molecular Architecture and Assembly Principles of Vibrio cholerae Biofilms SCIENCE Berk, V., Fong, J. C., Dempsey, G. T., Develioglu, O. N., Zhuang, X., Liphardt, J., Yildiz, F. H., Chu, S. 2012; 337 (6091): 236-239

  Abstract

  In their natural environment, microbes organize into communities held together by an extracellular matrix composed of polysaccharides and proteins. We developed an in vivo labeling strategy to allow the extracellular matrix of developing biofilms to be visualized with conventional and superresolution light microscopy. Vibrio cholerae biofilms displayed three distinct levels of spatial organization: cells, clusters of cells, and collections of clusters. Multiresolution imaging of living V. cholerae biofilms revealed the complementary architectural roles of the four essential matrix constituents: RbmA provided cell-cell adhesion; Bap1 allowed the developing biofilm to adhere to surfaces; and heterogeneous mixtures of Vibrio polysaccharide, RbmC, and Bap1 formed dynamic, flexible, and ordered envelopes that encased the cell clusters.

  View details for DOI 10.1126/science.1222981

  View details for Web of Science ID 000306323500059

  View details for PubMedID 22798614

  View details for PubMedCentralID PMC3513368

• Synchrotron Infrared Measurements of Protein Phosphorylation in Living Single PC12 Cells during Neuronal Differentiation ANALYTICAL CHEMISTRY Chen, L., Holman, H. N., Hao, Z., Bechtel, H. A., Martin, M. C., Wu, C., Chu, S. 2012; 84 (9): 4118-4125

  Abstract

  Protein phosphorylation is a post-translational modification that is essential for the regulation of many important cellular activities, including proliferation and differentiation. Current techniques for detecting protein phosphorylation in single cells often involve the use of fluorescence markers, such as antibodies or genetically expressed proteins. In contrast, infrared spectroscopy is a label-free and noninvasive analytical technique that can monitor the intrinsic vibrational signatures of chemical bonds. Here, we provide direct evidence that protein phosphorylation in individual living mammalian cells can be measured with synchrotron radiation-based Fourier transform-infrared (SR-FT-IR) spectromicroscopy. We show that PC12 cells stimulated with nerve growth factor (NGF) exhibit statistically significant temporal variations in specific spectral features, correlating with changes in protein phosphorylation levels and the subsequent development of neuron-like phenotypes in the cells. The spectral phosphorylation markers were confirmed by bimodal (FT-IR/fluorescence) imaging of fluorescently marked PC12 cells with sustained protein phosphorylation activity. Our results open up new possibilities for the label-free real-time monitoring of protein phosphorylation inside cells. Furthermore, the multimolecule sensitivity of this technique will be useful for unraveling the associated molecular changes during cellular signaling and response processes.

  View details for DOI 10.1021/ac300308x

  View details for Web of Science ID 000303349200037

  View details for PubMedID 22468902

• Synaptic proteins promote calcium-triggered fast transition from point contact to full fusion. eLife Diao, J., Grob, P., Cipriano, D. J., Kyoung, M., Zhang, Y., Shah, S., Nguyen, A., Padolina, M., Srivastava, A., Vrljic, M., Shah, A., Nogales, E., Chu, S., Brunger, A. T. 2012; 1

  Abstract

  The molecular underpinnings of synaptic vesicle fusion for fast neurotransmitter release are still unclear. Here, we used a single vesicle-vesicle system with reconstituted SNARE and synaptotagmin-1 proteoliposomes to decipher the temporal sequence of membrane states upon Ca(2+)-injection at 250-500 μM on a 100-ms timescale. Furthermore, detailed membrane morphologies were imaged with cryo-electron microscopy before and after Ca(2+)-injection. We discovered a heterogeneous network of immediate and delayed fusion pathways. Remarkably, all instances of Ca(2+)-triggered immediate fusion started from a membrane-membrane point-contact and proceeded to complete fusion without discernible hemifusion intermediates. In contrast, pathways that involved a stable hemifusion diaphragm only resulted in fusion after many seconds, if at all. When complexin was included, the Ca(2+)-triggered fusion network shifted towards the immediate pathway, effectively synchronizing fusion, especially at lower Ca(2+)-concentration. Synaptic proteins may have evolved to select this immediate pathway out of a heterogeneous network of possible membrane fusion pathways.DOI:http://dx.doi.org/10.7554/eLife.00109.001.

  View details for DOI 10.7554/eLife.00109

  View details for PubMedID 23240085

  View details for PubMedCentralID PMC3514886

• Post-Translational Modifications and Lipid Binding Profile of Insect Cell-Expressed Full-Length Mammalian Synaptotagmin 1 BIOCHEMISTRY Vrljic, M., Strop, P., Hill, R. C., Hansen, K. C., Chu, S., Brunger, A. T. 2011; 50 (46): 9998-10012

  Abstract

  Synaptotagmin 1 (Syt1) is a Ca(2+) sensor for SNARE-mediated, Ca(2+)-triggered synaptic vesicle fusion in neurons. It is composed of luminal, transmembrane, linker, and two Ca(2+)-binding (C2) domains. Here we describe expression and purification of full-length mammalian Syt1 in insect cells along with an extensive biochemical characterization of the purified protein. The expressed and purified protein is properly folded and has increased α-helical content compared to the C2AB fragment alone. Post-translational modifications of Syt1 were analyzed by mass spectrometry, revealing the same modifications of Syt1 that were previously described for Syt1 purified from brain extract or mammalian cell lines, along with a novel modification of Syt1, tyrosine nitration. A lipid binding screen with both full-length Syt1 and the C2AB fragments of Syt1 and Syt3 isoforms revealed new Syt1-lipid interactions. These results suggest a conserved lipid binding mechanism in which Ca(2+)-independent interactions are mediated via a lysine rich region of the C2B domain while Ca(2+)-dependent interactions are mediated via the Ca(2+)-binding loops.

  View details for DOI 10.1021/bi200998y

  View details for Web of Science ID 000296893700007

  View details for PubMedID 21928778

  View details for PubMedCentralID PMC3217305

• In vitro system capable of differentiating fast Ca2+-triggered content mixing from lipid exchange for mechanistic studies of neurotransmitter release PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Kyoung, M., Srivastava, A., Zhang, Y., Diao, J., Vrljic, M., Grob, P., Nogales, E., Chu, S., Brunger, A. T. 2011; 108 (29): E304-E313

  Abstract

  Understanding the molecular principles of synaptic vesicle fusion is a long-sought goal. It requires the development of a synthetic system that allows manipulations and observations not possible in vivo. Here, we report an in vitro system with reconstituted synaptic proteins that meets the long-sought goal to produce fast content release in the millisecond time regime upon Ca(2+) triggering. Our system simultaneously monitors both content and lipid exchange, and it starts from stable interacting pairs of donor and acceptor vesicles, mimicking the readily releasable pool of synaptic vesicles prior to an action potential. It differentiates between single-vesicle interaction, hemifusion, and complete fusion, the latter mimicking quantized neurotransmitter release upon exocytosis of synaptic vesicles. Prior to Ca(2+) injection, the system is in a state in which spontaneous fusion events between donor and acceptor vesicles are rare. Upon Ca(2+) injection, a rapid burst of complete fusion events emerges, followed by a biphasic decay. The present study focuses on neuronal SNAREs, the Ca(2+) sensor synaptotagmin 1, and the modulator complexin. However, other synaptic proteins could be added and their function examined. Ca(2+) triggering is cooperative, requiring the presence of synaptotagmin, whereas SNAREs alone do not produce a fast fusion burst. Manipulations of the system mimic effects observed in vivo. These results also show that neuronal SNAREs alone do not efficiently produce complete fusion, that the combination of SNAREs with synaptotagmin lowers the activation barriers to full fusion, and that complexin enhances this kinetic control.

  View details for DOI 10.1073/pnas.1107900108

  View details for Web of Science ID 000292876900007

  View details for PubMedID 21705659

  View details for PubMedCentralID PMC3141984

• Equivalence Principle and Gravitational Redshift PHYSICAL REVIEW LETTERS Hohensee, M. A., Chu, S., Peters, A., Mueller, H. 2011; 106 (15)

  Abstract

  We investigate leading order deviations from general relativity that violate the Einstein equivalence principle in the gravitational standard model extension. We show that redshift experiments based on matter waves and clock comparisons are equivalent to one another. Consideration of torsion balance tests, along with matter-wave, microwave, optical, and Mössbauer clock tests, yields comprehensive limits on spin-independent Einstein equivalence principle-violating standard model extension terms at the 10(-6) level.

  View details for DOI 10.1103/PhysRevLett.106.151102

  View details for Web of Science ID 000289358400004

  View details for PubMedID 21568541

• Towards Structural Biology with Single Molecules Experimental Biology Meeting 2011 Brunger, A., Strop, P., Vrljic, M., Chu, S., Weninger, K. FEDERATION AMER SOC EXP BIOL. 2011

  View details for Web of Science ID 000310708402359

• Three-dimensional molecular modeling with single molecule FRET JOURNAL OF STRUCTURAL BIOLOGY Brunger, A. T., Strop, P., Vrljic, M., Chu, S., Weninger, K. R. 2011; 173 (3): 497-505

  Abstract

  Single molecule fluorescence energy transfer experiments enable investigations of macromolecular conformation and folding by the introduction of fluorescent dyes at specific sites in the macromolecule. Multiple such experiments can be performed with different labeling site combinations in order to map complex conformational changes or interactions between multiple molecules. Distances that are derived from such experiments can be used for determination of the fluorophore positions by triangulation. When combined with a known structure of the macromolecule(s) to which the fluorophores are attached, a three-dimensional model of the system can be determined. However, care has to be taken to properly derive distance from fluorescence energy transfer efficiency and to recognize the systematic or random errors for this relationship. Here we review the experimental and computational methods used for three-dimensional modeling based on single molecule fluorescence resonance transfer, and describe recent progress in pushing the limits of this approach to macromolecular complexes.

  View details for DOI 10.1016/j.jsb.2010.09.004

  View details for Web of Science ID 000287681200010

  View details for PubMedID 20837146

  View details for PubMedCentralID PMC3051805

• Subnanometre single-molecule localization, registration and distance measurements NATURE Pertsinidis, A., Zhang, Y., Chu, S. 2010; 466 (7306): 647-U11

  Abstract

  Remarkable progress in optical microscopy has been made in the measurement of nanometre distances. If diffraction blurs the image of a point object into an Airy disk with a root-mean-squared (r.m.s.) size of s = 0.44lambda/2NA (approximately 90 nm for light with a wavelength of lambda = 600 nm and an objective lens with a numerical aperture of NA = 1.49), limiting the resolution of the far-field microscope in use to d = 2.4s approximately = 200 nm, additional knowledge about the specimen can be used to great advantage. For example, if the source is known to be two spatially resolved fluorescent molecules, the distance between them is given by the separation of the centres of the two fluorescence images. In high-resolution microwave and optical spectroscopy, there are numerous examples where the line centre is determined with a precision of less than 10(-6) of the linewidth. In contrast, in biological applications the brightest single fluorescent emitters can be detected with a signal-to-noise ratio of approximately 100, limiting the centroid localization precision to s(loc) > or = 1% (> or = 1 nm) of the r.m.s. size, s, of the microscope point spread function (PSF). Moreover, the error in co-localizing two or more single emitters is notably worse, remaining greater than 5-10% (5-10 nm) of the PSF size. Here we report a distance resolution of s(reg) = 0.50 nm (1sigma) and an absolute accuracy of s(distance) = 0.77 nm (1sigma) in a measurement of the separation between differently coloured fluorescent molecules using conventional far-field fluorescence imaging in physiological buffer conditions. The statistical uncertainty in the mean for an ensemble of identical single-molecule samples is limited only by the total number of collected photons, to s(loc) approximately 0.3 nm, which is approximately 3 x 10(-3) times the size of the optical PSF. Our method may also be used to improve the resolution of many subwavelength, far-field imaging methods such as those based on co-localization of molecules that are stochastically switched on in space. The improved resolution will allow the structure of large, multisubunit biological complexes in biologically relevant environments to be deciphered at the single-molecule level.

  View details for DOI 10.1038/nature09163

  View details for Web of Science ID 000280412100058

  View details for PubMedID 20613725

• Molecular mechanism of the synaptotagmin-SNARE interaction in Ca2+-triggered vesicle fusion NATURE STRUCTURAL & MOLECULAR BIOLOGY Vrljic, M., Strop, P., Ernst, J. A., Sutton, R. B., Chu, S., Brunger, A. T. 2010; 17 (3): 325-U92

  Abstract

  In neurons, SNAREs, synaptotagmin and other factors catalyze Ca(2+)-triggered fusion of vesicles with the plasma membrane. The molecular mechanism of this process, especially the interaction between synaptotagmin and SNAREs, remains an enigma. Here we characterized this interaction by single-molecule fluorescence microscopy and crystallography. The two rigid Ca(2+)-binding domains of synaptotagmin 3 (Syt3) undergo large relative motions in solution. Interaction with SNARE complex amplifies a particular state of the two domains that is further enhanced by Ca(2+). This state is represented by the first SNARE-induced Ca(2+)-bound crystal structure of a synaptotagmin fragment containing both domains. The arrangement of the Ca(2+)-binding loops of this structure of Syt3 matches that of SNARE-bound Syt1, suggesting a conserved feature of synaptotagmins. The loops resemble the membrane-interacting loops of certain viral fusion proteins in the postfusion state, suggesting unexpected similarities between both fusion systems.

  View details for DOI 10.1038/nsmb.1764

  View details for Web of Science ID 000275182700013

  View details for PubMedID 20173762

  View details for PubMedCentralID PMC2928146

• Single-molecule FRET-derived model of the synaptotagmin 1-SNARE fusion complex NATURE STRUCTURAL & MOLECULAR BIOLOGY Choi, U. B., Strop, P., Vrljic, M., Chu, S., Brunger, A. T., Weninger, K. R. 2010; 17 (3): 318-U84

  Abstract

  Synchronous neurotransmission is triggered when Ca(2+) binds to synaptotagmin 1 (Syt1), a synaptic-vesicle protein that interacts with SNAREs and membranes. We used single-molecule fluorescence resonance energy transfer (FRET) between synaptotagmin's two C2 domains to determine that their conformation consists of multiple states with occasional transitions, consistent with domains in random relative motion. SNARE binding results in narrower intrasynaptotagmin FRET distributions and less frequent transitions between states. We obtained an experimentally determined model of the elusive Syt1-SNARE complex using a multibody docking approach with 34 FRET-derived distances as restraints. The Ca(2+)-binding loops point away from the SNARE complex, so they may interact with the same membrane. The loop arrangement is similar to that of the crystal structure of SNARE-induced Ca(2+)-bound Syt3, suggesting a common mechanism by which the interaction between synaptotagmins and SNAREs aids in Ca(2+)-triggered fusion.

  View details for DOI 10.1038/nsmb.1763

  View details for Web of Science ID 000275182700012

  View details for PubMedID 20173763

  View details for PubMedCentralID PMC2922927

• A precision measurement of the gravitational redshift by the interference of matter waves NATURE Mueller, H., Peters, A., Chu, S. 2010; 463 (7283): 926-U96

  View details for DOI 10.1038/nature08776

  View details for Web of Science ID 000274582700041

• DNA Methylation Increases Nucleosome Compaction and Rigidity JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Choy, J. S., Wei, S., Lee, J. Y., Tan, S., Chu, S., Lee, T. 2010; 132 (6): 1782-?

  Abstract

  Cytosine methylation on CpG dinucleotides is an essential epigenetic modification in eukaryotes. How DNA methylation modulates nucleosome structure and dynamics has been a long-standing question. We implemented a single-molecule method to monitor the effects of DNA methylation on the structure and dynamics of mononucleosomes. Our studies show that DNA methylation induces a more compact and rigid nucleosome structure, providing a physical basis for how DNA methylation might contribute to regulating chromatin structure.

  View details for DOI 10.1021/ja910264z

  View details for Web of Science ID 000275085000025

  View details for PubMedID 20095602

  View details for PubMedCentralID PMC4167393

• Multiple native states reveal persistent ruggedness of an RNA folding landscape NATURE Solomatin, S. V., Greenfeld, M., Chu, S., Herschlag, D. 2010; 463 (7281): 681-U117

  Abstract

  According to the 'thermodynamic hypothesis', the sequence of a biological macromolecule defines its folded, active (or 'native') structure as a global energy minimum in the folding landscape. However, the enormous complexity of folding landscapes of large macromolecules raises the question of whether there is in fact a unique global minimum corresponding to a unique native conformation or whether there are deep local minima corresponding to alternative active conformations. The folding of many proteins is well described by two-state models, leading to highly simplified representations of protein folding landscapes with a single native conformation. Nevertheless, accumulating experimental evidence suggests a more complex topology of folding landscapes with multiple active conformations that can take seconds or longer to interconvert. Here we demonstrate, using single-molecule experiments, that an RNA enzyme folds into multiple distinct native states that interconvert on a timescale much longer than that of catalysis. These data demonstrate that severe ruggedness of RNA folding landscapes extends into conformational space occupied by native conformations.

  View details for DOI 10.1038/nature08717

  View details for Web of Science ID 000274193900040

  View details for PubMedID 20130651

  View details for PubMedCentralID PMC2818749

• A NEW PLATFORM FOR PROFILING ACTIVE PROTEASES WITH SINGLE-MOLECULE SENSITIVITY ASME 1st Global Congress on NanoEngineering for Medicine and Biology Dogan, M. Y., Revyakin, A., Park, S., Pertsinidis, A., Brown, C., Chu, S., Craik, C. S., Majumdar, A. AMER SOC MECHANICAL ENGINEERS. 2010: 77–78

  View details for Web of Science ID 000282210100035

• Molecular Mechanism of the Synaptotagmin-Snare Interaction in Ca2+-Triggered Vesicle Fusion Vrljic, M., Strop, P., Ernst, J. A., Sutton, R., Chu, S., Brunger, A. T. CELL PRESS. 2010: 439A

  View details for DOI 10.1016/j.bpj.2009.12.2382

  View details for Web of Science ID 000208762004192

• Single Molecule Study of Disassembly of SNARE Complex by NSF/alpha-SNAP Jung, J., Fenn, T. D., Chu, S., Brunger, A. T. CELL PRESS. 2010: 670A

  View details for DOI 10.1016/j.bpj.2009.12.3680

  View details for Web of Science ID 000208762006368

• Characterizing the Initial Encounter Complex in Cadherin Adhesion STRUCTURE Sivasankar, S., Zhang, Y., Nelson, W. J., Chu, S. 2009; 17 (8): 1075-1081

  Abstract

  Cadherins are Ca(2+)-dependent cell-cell adhesion proteins with an extracellular region of five domains (EC1 to EC5). Adhesion is mediated by "strand swapping" of a conserved tryptophan residue in position 2 between EC1 domains of opposing cadherins, but the formation of this structure is not well understood. Using single-molecule fluorescence resonance energy transfer and single-molecule force measurements with the atomic force microscope, we demonstrate that cadherins initially interact via EC1 domains without swapping tryptophan-2 to form a weak Ca(2+) dependent initial encounter complex that has 25% of the bond strength of a strand-swapped dimer. We suggest that cadherin dimerization proceeds via an induced fit mechanism where the monomers first form a tryptophan-2 independent initial encounter complex and then undergo subsequent conformational changes to form the final strand-swapped dimer.

  View details for DOI 10.1016/j.str.2009.06.012

  View details for Web of Science ID 000269229100008

  View details for PubMedID 19646884

• Noise-Immune Conjugate Large-Area Atom Interferometers PHYSICAL REVIEW LETTERS Chiow, S., Herrmann, S., Chu, S., Mueller, H. 2009; 103 (5)

  Abstract

  We present a pair of simultaneous conjugate Ramsey-Bordé atom interferometers using large (20variant Planck's over 2pik)-momentum transfer beam splitters, where variant Planck's over 2pik is the photon momentum. Simultaneous operation allows for common-mode rejection of vibrational noise. This allows us to surpass the enclosed space-time area of previous interferometers with a splitting of 20variant Planck's over 2pik by a factor of 2500. Using a splitting of 10variant Planck's over 2pik, we demonstrate a 3.4 ppb resolution in the measurement of the fine structure constant. Examples for applications in tests of fundamental laws of physics are given.

  View details for DOI 10.1103/PhysRevLett.103.050402

  View details for Web of Science ID 000268618300002

  View details for PubMedID 19792468

• Atom interferometry tests of local Lorentz invariance in gravity and electrodynamics PHYSICAL REVIEW D Chung, K., Chiow, S., Herrmann, S., Chu, S., Mueller, H. 2009; 80 (1)

  View details for DOI 10.1103/PhysRevD.80.016002

  View details for Web of Science ID 000268618600077

• Atom Interferometers with Scalable Enclosed Area PHYSICAL REVIEW LETTERS Mueller, H., Chiow, S., Herrmann, S., Chu, S. 2009; 102 (24)

  Abstract

  Bloch oscillations (i.e., coherent acceleration of matter waves by an optical lattice) and Bragg diffraction are integrated into light-pulse atom interferometers with large momentum splitting between the interferometer arms, and hence enhanced sensitivity. Simultaneous acceleration of both arms in the same internal states suppresses systematic effects, and simultaneously running a pair of interferometers suppresses the effect of vibrations. Ramsey-Bordé interferometers using four such Bloch-Bragg-Bloch beam splitters exhibit 15% contrast at 24variant Planck's over 2pik splitting, the largest so far (variant Planck's over 2pik is the photon momentum); single beam splitters achieve 88variant Planck's over 2pik. The prospects for reaching 100 s of variant Planck's over 2pik and applications such as gravitational wave sensors are discussed.

  View details for DOI 10.1103/PhysRevLett.102.240403

  View details for Web of Science ID 000267197900003

  View details for PubMedID 19658985

• Nanoparticle-Mediated Nonfluorescent Bonding of Microspheres to Atomic Force Microscope Cantilevers and Imaging Fluorescence from Bonded Cantilevers with Single Molecule Sensitivity NANO LETTERS Sivasankar, S., Chu, S. 2009; 9 (5): 2120-2124

  Abstract

  A technique to attach silica and glass microspheres onto silicon or silicon nitride cantilevers using silica nanoparticle sol-gel chemistry is presented and a method to image the fluorescence background from the bonded cantilevers with single molecule sensitivity is described. The silica nanoparticles polymerize to form a highly branched network that covalently link the microsphere and cantilever together. The bonding is carried out at room temperature which preserves the integrity of the cantilevers and their reflective coating. Comparison of cantilever and single dye molecule fluorescence demonstrates that the cantilevers are nonfluorescent at the single molecule level.

  View details for DOI 10.1021/nl900616y

  View details for Web of Science ID 000266157100070

  View details for PubMedID 19435383

• 6 W, 1 kHz linewidth, tunable continuous-wave near-infrared laser OPTICS EXPRESS Chiow, S., Herrmann, S., Mueller, H., Chu, S. 2009; 17 (7): 5246-5250

  Abstract

  A modified Coherent 899-21 titanium sapphire laser is injection locked to produce 6-6.5 W of single-frequency light at 852 nm. After closed-loop amplitude control and frequency stabilization to a high-finesse cavity, it delivers 4-4.5 W with < 1 kHz linewidth at the output of a single-mode fiber. The laser is tunable from about 700-1000 nm; up to 8 W should be possible at 750-810 nm.

  View details for Web of Science ID 000264747500038

  View details for PubMedID 19333288

• SINGLE MOLECULE STUDIES OF THE SYNAPTIC VESICLE FUSION MACHINERY 40th Annual Meeting of the American-Society-for-Neurochemistry Brunger, A. T., Weninger, K., Vrljic, M., Choi, U. B., Bowen, M. A., Chu, S. WILEY-BLACKWELL. 2009: 55–55

  View details for Web of Science ID 000263336800116

• Single Molecule Analysis of Group I Ribozyme Folding Reveals Pronounced Ruggedness Throughout Its Folding Landscape Solomatin, S., Greenfeld, M., Chu, S., Herschlag, D. CELL PRESS. 2009: 9A

  View details for Web of Science ID 000426275900044

• Relative Rearrangements Of Synaptotagmin3 C2A And C2B Domains Are Influenced ay Calcium, Lipids And SNARE Proteins Vrljic, M., Strop, P., Ernst, J., Sutton, R., Chu, S., Brunger, A. T. CELL PRESS. 2009: 358A–359A

  View details for Web of Science ID 000426353300855

• Resolving Cadherin Interactions at the Single Molecule Level Sivasankar, S., Zhang, Y., Nelson, W., Chu, S. CELL PRESS. 2009: 383A

  View details for Web of Science ID 000426354000055

• Resolving cadherin interactions and binding cooperativity at the single-molecule level PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Zhang, Y., Sivasankar, S., Nelson, W. J., Chu, S. 2009; 106 (1): 109-114

  Abstract

  The cadherin family of Ca(2+)-dependent cell adhesion proteins are critical for the morphogenesis and functional organization of tissues in multicellular organisms, but the molecular interactions between cadherins that are at the core of cell-cell adhesion are a matter of considerable debate. A widely-accepted model is that cadherins adhere in 3 stages. First, the functional unit of cadherin adhesion is a cis dimer formed by the binding of the extracellular regions of 2 cadherins on the same cell surface. Second, formation of low-affinity trans interactions between cadherin cis dimers on opposing cell surfaces initiates cell-cell adhesion. Third, lateral clustering of cadherins cooperatively strengthens intercellular adhesion. Evidence of these cadherin binding states during adhesion is, however, contradictory, and evidence for cooperativity is lacking. We used single-molecule structural (fluorescence resonance energy transfer) and functional (atomic force microscopy) assays to demonstrate directly that cadherin monomers interact via their N-terminal EC1 domain to form trans adhesive complexes. We could not detect the formation of cadherin cis dimers, but found that increasing the density of cadherin monomers cooperatively increased the probability of trans adhesive binding.

  View details for DOI 10.1073/pnas.0811350106

  View details for Web of Science ID 000262263900023

  View details for PubMedID 19114658

  View details for PubMedCentralID PMC2629205

• Single-Molecule Studies of the Neuronal SNARE Fusion Machinery ANNUAL REVIEW OF BIOCHEMISTRY Brunger, A. T., Weninger, K., Bowen, M., Chu, S. 2009; 78: 903-928

  Abstract

  SNAREs are essential components of the machinery for Ca(2+)-triggered fusion of synaptic vesicles with the plasma membrane, resulting in neurotransmitter release into the synaptic cleft. Although much is known about their biophysical and structural properties and their interactions with accessory proteins such as the Ca(2+) sensor synaptotagmin, their precise role in membrane fusion remains an enigma. Ensemble studies of liposomes with reconstituted SNAREs have demonstrated that SNAREs and accessory proteins can trigger lipid mixing/fusion, but the inability to study individual fusion events has precluded molecular insights into the fusion process. Thus, this field is ripe for studies with single-molecule methodology. In this review, we discuss applications of single-molecule approaches to observe reconstituted SNAREs, their complexes, associated proteins, and their effect on biological membranes. Some of the findings are provocative, such as the possibility of parallel and antiparallel SNARE complexes or of vesicle docking with only syntaxin and synaptobrevin, but have been confirmed by other experiments.

  View details for DOI 10.1146/annurev.biochem.77.070306.103621

  View details for Web of Science ID 000268069200032

  View details for PubMedID 19489736

  View details for PubMedCentralID PMC2854664

• ATOM INTERFEROMETRY EXPERIMENTS IN FUNDAMENTAL PHYSICS 7th Symposium on Frequency Standards and Metrology Chiow, S. W., Herrmann, S., Chu, S., Mueller, H. WORLD SCIENTIFIC PUBL CO PTE LTD. 2009: 53–61

  View details for Web of Science ID 000270540200005

• Direct measurement of tertiary contact cooperativity in RNA folding JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Sattint, B. D., Zhao, W., Travers, K., Chut, S., Herschlag, D. 2008; 130 (19): 6085-?

  Abstract

  All structured biological macromolecules must overcome the thermodynamic folding problem to populate a unique functional state among a vast ensemble of unfolded and alternate conformations. The exploration of cooperativity in protein folding has helped reveal and distinguish the underlying mechanistic solutions to this folding problem. Analogous dissections of RNA tertiary stability remain elusive, however, despite the central biological importance of folded RNA molecules and the potential to reveal fundamental properties of structured macromolecules via comparisons of protein and RNA folding. We report a direct quantitative measure of tertiary contact cooperativity in a folded RNA. We precisely measured the stability of an independently folding P4-P6 domain from the Tetrahymena thermophila group I intron by single molecule fluorescence resonance energy transfer (smFRET). Using wild-type and mutant RNAs, we found that cooperativity between the two tertiary contacts enhances P4-P6 stability by 3.2 +/- 0.2 kcal/mol.

  View details for DOI 10.1021/ja800919q

  View details for Web of Science ID 000255620200014

  View details for PubMedID 18429611

  View details for PubMedCentralID PMC2835547

• Atom interferometry with up to 24-photon-momentum-transfer beam splitters PHYSICAL REVIEW LETTERS Mueller, H., Chiow, S., Long, Q., Herrmann, S., Chu, S. 2008; 100 (18)

  Abstract

  We present up to 24-photon Bragg diffraction as a beam splitter in light-pulse atom interferometers to achieve the largest splitting in momentum space so far. Relative to the 2-photon processes used in the most sensitive present interferometers, these large momentum transfer beam splitters increase the phase shift 12-fold for Mach-Zehnder (MZ) and 144-fold for Ramsey-Bordé (RB) geometries. We achieve a high visibility of the interference fringes (up to 52% for MZ or 36% for RB) and long pulse separation times that are possible only in atomic fountain setups. As the atom's internal state is not changed, important systematic effects can cancel.

  View details for DOI 10.1103/PhysRevLett.100.180405

  View details for Web of Science ID 000255771400005

  View details for PubMedID 18518355

• Atom-wave diffraction between the Raman-Nath and the Bragg regime: Effective Rabi frequency, losses, and phase shifts PHYSICAL REVIEW A Mueller, H., Chiow, S., Chu, S. 2008; 77 (2)

  View details for DOI 10.1103/PhysRevA.77.023609

  View details for Web of Science ID 000253763900112

• Accessory proteins stabilize the acceptor complex for synaptobrevin, the 1 : 1 syntaxin/SNAP-25 complex STRUCTURE Weninger, K., Bowen, M. E., Choi, U. B., Chu, S., Brunger, A. T. 2008; 16 (2): 308-320

  Abstract

  Syntaxin/SNAP-25 interactions precede assembly of the ternary SNARE complex that is essential for neurotransmitter release. This binary complex has been difficult to characterize by bulk methods because of the prevalence of a 2:1 dead-end species. Here, using single-molecule fluorescence, we find the structure of the 1:1 syntaxin/SNAP-25 binary complex is variable, with states changing on the second timescale. One state corresponds to a parallel three-helix bundle, whereas other states show one of the SNAP-25 SNARE domains dissociated. Adding synaptobrevin suppresses the dissociated helix states. Remarkably, upon addition of complexin, Munc13, Munc18, or synaptotagmin, a similar effect is observed. Thus, the 1:1 binary complex is a dynamic acceptor for synaptobrevin binding, and accessory proteins stabilize this acceptor. In the cellular environment the binary complex is actively maintained in a configuration where it can rapidly interact with synaptobrevin, so formation is not likely a limiting step for neurotransmitter release.

  View details for DOI 10.1016/j.str.2007.12.010

  View details for Web of Science ID 000253219400015

  View details for PubMedID 18275821

  View details for PubMedCentralID PMC2856644

• Atom-interferometry tests of the isotropy of post-Newtonian gravity PHYSICAL REVIEW LETTERS Mueller, H., Chiow, S., Herrmann, S., Chu, S., Chung, K. 2008; 100 (3)

  Abstract

  We present a test of the local Lorentz invariance of post-Newtonian gravity by monitoring Earth's gravity with a Mach-Zehnder atom interferometer that features a resolution of up to 8 x 10{-9}g/sqrt[Hz], the highest reported thus far. Expressed within the standard model extension (SME) or Nordtvedt's anisotropic universe model, the analysis limits four coefficients describing anisotropic gravity at the ppb level and three others, for the first time, at the 10 ppm level. Using the SME we explicitly demonstrate how the experiment actually compares the isotropy of gravity and electromagnetism.

  View details for DOI 10.1103/PhysRevLett.100.031101

  View details for Web of Science ID 000252698100013

  View details for PubMedID 18232958

• Multiphoton- and simultaneous conjugate Ramsey-Borde atom interferometers 3rd Mexican Meeting on Mathematical and Experimental Physics Mueller, H., Chiow, S., Herrmann, S., Chu, S. AMER INST PHYSICS. 2008: 291–301

  View details for Web of Science ID 000253567700023

• Nanosecond electro-optical switching with a repetition rate above 20 MHz REVIEW OF SCIENTIFIC INSTRUMENTS Mueller, H., Chiow, S., Herrmann, S., Chu, S. 2007; 78 (12)

  Abstract

  We describe an electro-optical switch based on a commercial electro-optic modulator (modified for high-speed operation) and a 340 V pulser having a rise time of 2.2 ns (at 250 V). It can produce arbitrary pulse patterns with an average repetition rate beyond 20 MHz. It uses a grounded-grid triode driven by transmitting power transistors. We discuss variations that enable analog operation, use the step-recovery effect in bipolar transistors, or offer other combinations of output voltage, size, and cost.

  View details for DOI 10.1063/1.2822101

  View details for Web of Science ID 000251988300030

  View details for PubMedID 18163741

• Thiostrepton inhibition of tRNA delivery to the ribosome RNA-A PUBLICATION OF THE RNA SOCIETY Gonzalez, R. L., Chu, S., Puglisi, J. D. 2007; 13 (12): 2091-2097

  Abstract

  Ribosome-stimulated hydrolysis of guanosine-5'-triphosphate (GTP) by guanosine triphosphatase (GTPase) translation factors drives protein synthesis by the ribosome. Allosteric coupling of GTP hydrolysis by elongation factor Tu (EF-Tu) at the ribosomal GTPase center to messenger RNA (mRNA) codon:aminoacyl-transfer RNA (aa-tRNA) anticodon recognition at the ribosomal decoding site is essential for accurate and rapid aa-tRNA selection. Here we use single-molecule methods to investigate the mechanism of action of the antibiotic thiostrepton and show that the GTPase center of the ribosome has at least two discrete functions during aa-tRNA selection: binding of EF-Tu(GTP) and stimulation of GTP hydrolysis by the factor. We separate these two functions of the GTPase center and assign each to distinct, conserved structural regions of the ribosome. The data provide a specific model for the coupling between the decoding site and the GTPase center during aa-tRNA selection as well as a general mechanistic model for ribosome-stimulated GTP hydrolysis by GTPase translation factors.

  View details for DOI 10.1261/rna.499407

  View details for PubMedID 17951333

• Extended-cavity diode lasers with tracked resonances APPLIED OPTICS Chiow, S., Long, Q., Vo, C., Mueller, H., Chu, S. 2007; 46 (33): 7997-8001

  Abstract

  We present a painless, almost-free upgrade to present extended-cavity diode lasers (ECDLs) that improves the long-term mode-hop-free performance by stabilizing the resonance of the internal cavity to the external cavity. This stabilization is based on the observation that the frequency or amplitude noise of the ECDL is lowest at the optimum laser diode temperature or injection current. Thus, keeping the diode current at the level where the noise is lowest ensures mode-hop-free operation within one of the stable regions of the mode chart, even if these should drift due to external influences. This method can be applied directly to existing laser systems without modifying the optical setup. We demonstrate the method in two ECDLs stabilized to vapor cells at 852 and 895 nm wavelengths. We achieve long-term mode-hop-free operation and low noise at low power consumption, even with an inexpensive non-antireflection-coated diode.

  View details for Web of Science ID 000251830400005

  View details for PubMedID 18026536

• Fluctuations of transfer RNAs between classical and hybrid states BIOPHYSICAL JOURNAL Kim, H. D., Puglisi, J. D., Chu, S. 2007; 93 (10): 3575-3582

  Abstract

  Adjacent transfer RNAs (tRNAs) in the A- and P-sites of the ribosome are in dynamic equilibrium between two different conformations called classical and hybrid states before translocation. Here, we have used single-molecule fluorescence resonance energy transfer to study the effect of Mg(2+) on tRNA dynamics with and without an acetyl group on the A-site tRNA. When the A-site tRNA is not acetylated, tRNA dynamics do not depend on [Mg(2+)], indicating that the relative positions of the substrates for peptide-bond formation are not affected by Mg(2+). In sharp contrast, when the A-site tRNA is acetylated, Mg(2+) lengthens the lifetime of the classical state but does not change the lifetime of the hybrid state. Based on these findings, the classical state resembles a state with direct stabilization of tertiary structure by Mg(2+) ions whereas the hybrid state resembles a state with little Mg(2+)-assisted stabilization. The antibiotic viomycin, a translocation inhibitor, suppresses tRNA dynamics, suggesting that the enhanced fluctuations of tRNAs after peptide-bond formation drive spontaneous attempts at translocation by the ribosome.

  View details for DOI 10.1529/biophysj.107.109884

  View details for PubMedID 17693476

• A functional dynein-microtubule network is required for NGF signaling through the Rap1/MAPK pathway TRAFFIC Wu, C., Ramirez, A., Cui, B., Ding, J., Delcroix, J. M., Valletta, J. S., Liu, J., Yang, Y., Chu, S., Mobley, W. C. 2007; 8 (11): 1503-1520

  Abstract

  Rap1 transduces nerve growth factor (NGF)/tyrosine receptor kinase A (TrkA) signaling in early endosomes, leading to sustained activation of the p44/p42 mitogen-activated protein kinases (MAPK1/2). However, the mechanisms by which NGF, TrkA and Rap1 are trafficked to early endosomes are poorly defined. We investigated trafficking and signaling of NGF, TrkA and Rap1 in PC12 cells and in cultured rat dorsal root ganglion (DRG) neurons. Herein, we show a role for both microtubule- and dynein-based transport in NGF signaling through MAPK1/2. NGF treatment resulted in trafficking of NGF, TrkA and Rap1 to early endosomes in the perinuclear region of PC12 cells where sustained activation of MAPK1/2 was observed. Disruption of microtubules with nocodazole in PC12 cells had no effect on the activation of TrkA and Ras. However, it disrupted intracellular trafficking of TrkA and Rap1. Moreover, NGF-induced activation of Rap1 and sustained activation of MAPK1/2 were markedly suppressed. Inhibition of dynein activity through overexpression of dynamitin (p50) blocked trafficking of Rap1 and the sustained phase of MAPK1/2 activation in PC12 cells. Remarkably, even in the continued presence of NGF, mature DRG neurons that overexpressed p50 became atrophic and most (>80%) developing DRG neurons died. Dynein- and microtubule-based transport is thus necessary for TrkA signaling to Rap1 and MAPK1/2.

  View details for DOI 10.1111/j.1600-0854.2007.00636.x

  View details for Web of Science ID 000250363800005

  View details for PubMedID 17822405

• Optical bonding using silica nanoparticle sol-gel chemistry NANO LETTERS Sivasankar, S., Chu, S. 2007; 7 (10): 3031-3034

  Abstract

  A simple method is described to bond optical components using silica nanoparticle sol-gel chemistry. The silica nanoparticles polymerize into highly branched networks that link the surfaces together. The nanoparticle mediated bonding has several advantages to currently used optical joining technologies. The bonding is a room-temperature process and does not require any clean room facilities. The bonded interface has a high mechanical strength and low scattering. The bonding is resistant to organic solvents on silylation with hydrophobic surface groups. This method achieves 100% successful bonding rates between soda-lime glass slides. The bond-setting time can be tailored to allow time for precision optical alignment.

  View details for DOI 10.1021/nl071492h

  View details for Web of Science ID 000250143400017

  View details for PubMedID 17854226

• One at a time, live tracking of NGF axonal transport using quantum dots PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Cui, B., Wu, C., Chen, L., Ramirez, A., Bearer, E. L., Li, W., Mobley, W. C., Chu, S. 2007; 104 (34): 13666-13671

  Abstract

  Retrograde axonal transport of nerve growth factor (NGF) signals is critical for the survival, differentiation, and maintenance of peripheral sympathetic and sensory neurons and basal forebrain cholinergic neurons. However, the mechanisms by which the NGF signal is propagated from the axon terminal to the cell body are yet to be fully elucidated. To gain insight into the mechanisms, we used quantum dot-labeled NGF (QD-NGF) to track the movement of NGF in real time in compartmentalized culture of rat dorsal root ganglion (DRG) neurons. Our studies showed that active transport of NGF within the axons was characterized by rapid, unidirectional movements interrupted by frequent pauses. Almost all movements were retrograde, but short-distance anterograde movements were occasionally observed. Surprisingly, quantitative analysis at the single molecule level demonstrated that the majority of NGF-containing endosomes contained only a single NGF dimer. Electron microscopic analysis of axonal vesicles carrying QD-NGF confirmed this finding. The majority of QD-NGF was found to localize in vesicles 50-150 nm in diameter with a single lumen and no visible intralumenal membranous components. Our findings point to the possibility that a single NGF dimer is sufficient to sustain signaling during retrograde axonal transport to the cell body.

  View details for DOI 10.1073/pnas.0706192104

  View details for Web of Science ID 000249064700027

  View details for PubMedID 17698956

  View details for PubMedCentralID PMC1959439

• The role of fluctuations in tRNA selection by the ribosome PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Lee, T., Blanchard, S. C., Kim, H. D., Puglisi, J. D., Chu, S. 2007; 104 (34): 13661-13665

  Abstract

  The detailed mechanism of how the ribosome decodes protein sequence information with an abnormally high accuracy, after 40 years of study, remains elusive. A critical element in selecting correct transfer RNA (tRNA) transferring correct amino acid is "induced fit" between the ribosome and tRNA. By using single-molecule methods, the induced fit mechanism is shown to position favorably the correct tRNA after initial codon recognition. We provide evidence that this difference in positioning and thermal fluctuations constitutes the primary mechanism for the initial selection of tRNA. This work demonstrates thermal fluctuations playing a critical role in the substrate selection by an enzyme.

  View details for DOI 10.1073/pnas.0705988104

  View details for PubMedID 17699629

• Measuring the folding transition time of single RNA molecules BIOPHYSICAL JOURNAL Lee, T., Lapidus, L. J., Zhao, W., Travers, K. J., Herschlag, D., Chu, S. 2007; 92 (9): 3275-3283

  Abstract

  We describe a new, time-apertured photon correlation method for resolving the transition time between two states of RNA in folding--i.e., the time of the transition between states rather than the time spent in each state. Single molecule fluorescence resonance energy transfer and fluorescence correlation spectroscopy are used to obtain these measurements. Individual RNA molecules are labeled with fluorophores such as Cy3 and Cy5. Those molecules are then immobilized on a surface and observed for many seconds during which time the molecules spontaneously switch between two conformational states with different levels of flourescence resonance energy transfer efficiency. Single photons are counted from each fluorophore and cross correlated in a small window around a transition. The average of over 1000 cross correlations can be fit to a polynomial, which can determine transition times as short as the average photon emission interval. We applied the method to the P4-P6 domain of the Tetrahymena group I self-splicing intron to yield the folding transition time of 240 micros. The unfolding time is found to be too short to measure with this method.

  View details for DOI 10.1529/biophysj.106.094623

  View details for Web of Science ID 000245544100034

  View details for PubMedID 17307831

  View details for PubMedCentralID PMC1852359

• The individualistic dynamics of entangled DNA in solution MACROMOLECULES Teixeira, R. E., Dambal, A. K., Richter, D. H., Shaqfeh, E. S., Chu, S. 2007; 40 (7): 2461-2476

  View details for DOI 10.1021/ma062932e

  View details for Web of Science ID 000245208400024

• Peptide bond formation destabilizes Shine-Dalgarno interaction on the ribosome NATURE Uemura, S., Dorywalska, M., Lee, T., Kim, H. D., Puglisi, J. D., Chu, S. 2007; 446 (7134): 454-457

  Abstract

  The ribosome is a molecular machine that translates the genetic code contained in the messenger RNA into an amino acid sequence through repetitive cycles of transfer RNA selection, peptide bond formation and translocation. Here we demonstrate an optical tweezer assay to measure the rupture force between a single ribosome complex and mRNA. The rupture force was compared between ribosome complexes assembled on an mRNA with and without a strong Shine-Dalgarno (SD) sequence-a sequence found just upstream of the coding region of bacterial mRNAs, involved in translation initiation. The removal of the SD sequence significantly reduced the rupture force in complexes carrying an aminoacyl tRNA, Phe-tRNA(Phe), in the A site, indicating that the SD interactions contribute significantly to the stability of the ribosomal complex on the mRNA before peptide bond formation. In contrast, the presence of a peptidyl tRNA analogue, N-acetyl-Phe-tRNA(Phe), in the A site, which mimicked the post-peptidyl transfer state, weakened the rupture force as compared to the complex with Phe-tRNA(Phe), and the resultant force was the same for both the SD-containing and SD-deficient mRNAs. These results suggest that formation of the first peptide bond destabilizes the SD interaction, resulting in the weakening of the force with which the ribosome grips an mRNA. This might be an important requirement to facilitate movement of the ribosome along mRNA during the first translocation step.

  View details for DOI 10.1038/nature05625

  View details for PubMedID 17377584

• Retrolinkin, a membrane protein, plays an important role in retrograde axonal transport PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Liu, J., Ding, J., Wu, C., Bhagavatula, P., Cui, B., Chu, S., Mobley, W. C., Yang, Y. 2007; 104 (7): 2223-2228

  Abstract

  Retrograde axonal transport plays an important role in the maintenance of neuronal functions, but the mechanism is poorly defined partly because the constituents of the retrograde transport system and their interactions have yet to be elucidated. Of special interest is how dynein/dynactin motor proteins interact with membrane cargoes. Here, we report that an endosomal vesicle protein, termed retrolinkin, functions as a receptor tethering vesicles to dynein/dynactin through BPAG1n4. Retrolinkin, a membrane protein highly enriched in neuronal endosomes, binds directly to BPAG1n4. Deletion of retrolinkin membrane-association domains disrupts retrograde vesicular transport, recapitulating the BPAG1 null phenotype. We propose that retrolinkin acts with BPAG1n4 to specifically regulate retrograde axonal transport. Our work lays the foundation for understanding fundamental issues of axonal transport and provides insights into the molecular mechanisms underlying human neurodegenerative disorders.

  View details for DOI 10.1073/pnas.0602222104

  View details for Web of Science ID 000244438500035

  View details for PubMedID 17287360

  View details for PubMedCentralID PMC1892971

• Single molecule studies of SNARE-dependent fusion 51st Annual Meeting of the Biophysical-Society Brunger, A., Chu, S., Bowen, M., Weninger, K., Vrljic, M. CELL PRESS. 2007: 375A–375A

  View details for Web of Science ID 000243972402305

• PHYS 70-Optomechanical measurements of DNA interaction at the single molecule level Sivasankar, S., Chu, S. AMER CHEMICAL SOC. 2006

  View details for Web of Science ID 000207781609592

• PHYS 502-Structural and kinetics fluctuations of the ribosome Mohanty, U., Spasic, A., Mohanty, S., Sanyasi, S., Chu, S. AMER CHEMICAL SOC. 2006

  View details for Web of Science ID 000207781609052

• Gene targeting of GAN in mouse causes a toxic accumulation of microtubule-associated protein 8 and impaired retrograde axonal transport HUMAN MOLECULAR GENETICS Ding, J. Q., Allen, E., Wang, W., Valle, A., Wu, C. B., Nardine, T., Cui, B. X., Yi, J., Taylor, A., Jeon, N. L., Chu, S., So, Y., Vogel, H., Tolwani, R., Mobley, W., Yang, Y. M. 2006; 15 (9): 1451-1463

  Abstract

  Mutations in gigaxonin were identified in giant axonal neuropathy (GAN), an autosomal recessive disorder. To understand how disruption of gigaxonin's function leads to neurodegeneration, we ablated the gene expression in mice using traditional gene targeting approach. Progressive neurological phenotypes and pathological lesions that developed in the GAN null mice recapitulate characteristic human GAN features. The disruption of gigaxonin results in an impaired ubiquitin-proteasome system leading to a substantial accumulation of a novel microtubule-associated protein, MAP8, in the null mutants. Accumulated MAP8 alters the microtubule network, traps dynein motor protein in insoluble structures and leads to neuronal death in cultured wild-type neurons, which replicates the process occurring in GAN null mutants. Defective axonal transport is evidenced by the in vitro assays and is supported by vesicular accumulation in the GAN null neurons. We propose that the axonal transport impairment may be a deleterious consequence of accumulated, toxic MAP8 protein.

  View details for DOI 10.1093/hmg/ddl069

  View details for PubMedID 16565160

• Phase-locked, low-noise, frequency agile titanium: sapphire lasers for simultaneous atom interferometers OPTICS LETTERS Muller, H., Chiow, S. W., Long, Q., Chu, S. 2006; 31 (2): 202-204

  Abstract

  We demonstrate a laser system consisting of a >1.6 W titanium:sapphire laser that is phase locked to another free-running titanium:sapphire laser at a wavelength of 852 nm with a phase noise of -138 dBc/Hz at 1 MHz from the carrier, using an intracavity electro-optic phase modulator. The residual phase variance is 2.5 x 10(-8) rad2 integrated from 1 Hz to 10 kHz. This system can phase-continuously change the offset frequency within 200 ns with frequency steps up to 4 MHz. Simultaneous atom interferometers can make full use of this ultralow phase noise in differential measurements, where influences from the vibration of optics are greatly suppressed in common mode.

  View details for Web of Science ID 000234665000021

  View details for PubMedID 16441030

• Active sub-Rayleigh alignment of parallel or antiparallel laser beams OPTICS LETTERS Muller, H., Chiow, S. W., Long, Q., Vo, C., Chu, S. 2005; 30 (24): 3323-3325

  Abstract

  We measure and stabilize the relative angle of parallel and antiparallel laser beams to 5 nrad/(square root of)Hz resolution by comparing the phases of radio frequency beat notes on a quadrant photodetector. The absolute accuracy is 5.1 and 2.1 microrad for antiparallel and parallel beams, respectively, which is more than 6 and 16 times below the Rayleigh criterion.

  View details for Web of Science ID 000233827000021

  View details for PubMedID 16389819

• Ion atmosphere around nucleic acid JOURNAL OF PHYSICAL CHEMISTRY B Taubes, C. H., Mohanty, U., Chu, S. 2005; 109 (45): 21267–72

  Abstract

  The poyion-ion preferential interaction coefficient Gamma describes the exclusion of coions and accumulations of counterions in the vicinity of a polyion in an aqueous solution. We give tight upper and lower bounds for Gamma when the polyion can be modeled by a cylinder of infinite length but of arbitrary charge density. This case can be used as a model for long strands of DNA or RNA in an aqueous solution containing univalent cations. The salt dependence of Gamma is predicted from low to intermediate and high salt concentrations. We also indicate how the bounds for the infinite polyion can be exploited to place bounds for polyions of length greater than a constant on the order of the inverse Debye screening length.

  View details for DOI 10.1021/jp051590w

  View details for Web of Science ID 000233280600005

  View details for PubMedID 16853757

• Parametric amplification of matter waves in periodically translated optical lattices PHYSICAL REVIEW LETTERS Gemelke, N., Sarajlic, E., Bidel, Y., Hong, S., Chu, S. 2005; 95 (17)

  Abstract

  We observe the sudden growth of small classes of Bloch waves from atomic Bose-Einstein condensates held in periodically translated optical lattices. The effect is explained by narrowband parametric amplification of Bloch waves from noise, due to phase-matched scattering of atom pairs out of the condensate. Amplification occurs above a well-defined modulation threshold, described by dynamic shaping of single-particle band structure.

  View details for DOI 10.1103/PhysRevLett.95.170404

  View details for Web of Science ID 000232724400004

  View details for PubMedID 16383801

• Ion atmosphere of three-way junction nucleic acid Mohanty, U., Mohanty, U., Kim, H. D., Chu, S. AMER CHEMICAL SOC. 2005: U1224–U1225

  View details for Web of Science ID 000236797302462

• Phase shifts in precision atom interferometry due to the localization of atoms and optical fields PHYSICAL REVIEW A Wicht, A., Sarajlic, E., Hensley, J. M., Chu, S. 2005; 72 (2)

  View details for DOI 10.1103/PhysRevA.72.023602

  View details for Web of Science ID 000231564200153

• Characteristic periodic motion of polymers in shear flow PHYSICAL REVIEW LETTERS Schroeder, C. M., Teixeira, R. E., Shaqfeh, E. S., Chu, S. 2005; 95 (1)

  Abstract

  The motion of both free and tethered polymer molecules as well as rigid Brownian rods in unbound shear flow is found to be characterized by a clear periodicity or tumbling frequency. Periodicity is shown using a combination of single molecule DNA experiments and computer simulations. In all cases, we develop scaling laws for this behavior and demonstrate that the frequency of characteristic periodic motion scales sublinearly with flow rate.

  View details for DOI 10.1103/PhysRevLett.95.018301

  View details for Web of Science ID 000230275500075

  View details for PubMedID 16090661

• Single-molecule studies of synaptotagmin and complexin binding to the SNARE complex BIOPHYSICAL JOURNAL Bowen, M. E., Weninger, K., Ernst, J., Chu, S., Brunger, A. T. 2005; 89 (1): 690-702

  Abstract

  The assembly of multiprotein complexes at the membrane interface governs many signaling processes in cells. However, very few methods exist for obtaining biophysical information about protein complex formation at the membrane. We used single molecule fluorescence resonance energy transfer to study complexin and synaptotagmin interactions with the SNARE complex in deposited lipid bilayers. Using total internal reflectance microscopy, individual binding events at the membrane could be resolved despite an excess of unbound protein in solution. Fluorescence resonance energy transfer (FRET)-efficiency derived distances for the complexin-SNARE interaction were consistent with the crystal structure of the complexin-SNARE complex. The unstructured N-terminal region of complexin showed broad distributions of FRET efficiencies to the SNARE complex, suggesting that information on conformational variability can be obtained from FRET efficiency distributions. The low-affinity interaction of synaptotagmin with the SNARE complex changed dramatically upon addition of Ca2+ with high FRET efficiency interactions appearing between the C2B domain and linker domains of synaptotagmin and the membrane proximal portion of the SNARE complex. These results demonstrate that single molecule FRET can be used as a "spectroscopic ruler" to simultaneously gain structural and kinetic information about transient multiprotein complexes at the membrane interface.

  View details for DOI 10.1529/biophysj.104.054064

  View details for Web of Science ID 000230114500067

  View details for PubMedID 15821166

  View details for PubMedCentralID PMC1366567

• Dynamics of DNA in the flow-gradient plane of steady shear flow: Observations and simulations MACROMOLECULES Schroeder, C. M., Teixeira, R. E., Shaqfeh, E. S., Chu, S. 2005; 38 (5): 1967-1978

  View details for DOI 10.1021/ma0480796

  View details for Web of Science ID 000227448200059

• Shear thinning and tumbling dynamics of single polymers in the flow-gradient plane MACROMOLECULES Teixeira, R. E., Babcock, H. P., Shaqfeh, E. S., Chu, S. 2005; 38 (2): 581-592

  View details for DOI 10.1021/ma0480771

  View details for Web of Science ID 000226466700047

• Site-specific labeling of the ribosome for single-molecule spectroscopy NUCLEIC ACIDS RESEARCH Dorywalska, M., Blanchard, S. C., Gonzalez, R. L., Kim, H. D., Chu, S., Puglisi, J. D. 2005; 33 (1): 182-189

  Abstract

  Single-molecule fluorescence spectroscopy can reveal mechanistic and kinetic details that may not be observed in static structural and bulk biochemical studies of protein synthesis. One approach requires site-specific and stable attachment of fluorophores to the components of translation machinery. Fluorescent tagging of the ribosome is a prerequisite for the observation of dynamic changes in ribosomal conformation during translation using fluorescence methods. Modifications of the ribosomal particle are difficult due to its complexity and high degree of sequence and structural conservation. We have developed a general method to label specifically the prokaryotic ribosome by hybridization of fluorescent oligonucleotides to mutated ribosomal RNA. Functional, modified ribosomes can be purified as a homogenous population, and fluorescence can be monitored from labeled ribosomal complexes immobilized on a derivatized quartz surface.

  View details for DOI 10.1093/nar/gki151

  View details for PubMedID 15647501

• Effect of hydrodynamic interactions on DNA dynamics in extensional flow: Simulation and single molecule experiment MACROMOLECULES Schroeder, C. M., Shaqfeh, E. S., Chu, S. 2004; 37 (24): 9242-9256

  View details for DOI 10.1021/ma049461l

  View details for Web of Science ID 000225371200055

• Single molecule observation of liposome-bilayer fusion thermally induced by soluble N-ethyl maleimide sensitive-factor attachment protein receptors (SNAREs) BIOPHYSICAL JOURNAL Bowen, M. E., Weninger, K., Brunger, A. T., Chu, S. 2004; 87 (5): 3569-3584

  Abstract

  A single molecule fluorescence assay is presented for studying the mechanism of soluble N-ethyl maleimide sensitive-factor attachment protein receptors (SNAREs)-mediated liposome fusion to supported lipid bilayers. The three neuronal SNAREs syntaxin-1A, synaptobrevin-II (VAMP), and SNAP-25A were expressed separately, and various dye-labeled combinations of the SNAREs were tested for their ability to dock liposomes and induce fusion. Syntaxin and synaptobrevin in opposing membranes were both necessary and sufficient to dock liposomes to supported bilayers and to induce thermally activated fusion. As little as one SNARE interaction was sufficient for liposome docking. Fusion of docked liposomes with the supported bilayer was monitored by the dequenching of soluble fluorophores entrapped within the liposomes. Fusion was stimulated by illumination with laser light, and the fusion probability was enhanced by raising the ambient temperature from 22 to 37 degrees C, suggesting a thermally activated process. Surprisingly, SNAP-25 had little effect on docking efficiency or the probability of thermally induced fusion. Interprotein fluorescence resonance energy transfer experiments suggest the presence of other conformational states of the syntaxin*synaptobrevin interaction in addition to those observed in the crystal structure of the SNARE complex. Furthermore, although SNARE complexes involved in liposome docking preferentially assemble into a parallel configuration, both parallel and antiparallel configurations were observed.

  View details for DOI 10.1529/biophysj.104.048637

  View details for Web of Science ID 000224732500057

  View details for PubMedID 15347585

  View details for PubMedCentralID PMC1304822

• tRNA selection and kinetic proofreading in translation NATURE STRUCTURAL & MOLECULAR BIOLOGY Blanchard, S. C., Gonzalez, R. L., Kim, H. D., Chu, S., Puglisi, J. D. 2004; 11 (10): 1008-1014

  Abstract

  Using single-molecule methods we observed the stepwise movement of aminoacyl-tRNA (aa-tRNA) into the ribosome during selection and kinetic proofreading using single-molecule fluorescence resonance energy transfer (smFRET). Intermediate states in the pathway of tRNA delivery were observed using antibiotics and nonhydrolyzable GTP analogs. We identified three unambiguous FRET states corresponding to initial codon recognition, GTPase-activated and fully accommodated states. The antibiotic tetracycline blocks progression of aa-tRNA from the initial codon recognition state, whereas cleavage of the sarcin-ricin loop impedes progression from the GTPase-activated state. Our data support a model in which ribosomal recognition of correct codon-anticodon pairs drives rotational movement of the incoming complex of EF-Tu-GTP-aa-tRNA toward peptidyl-tRNA during selection on the ribosome. We propose a mechanistic model of initial selection and proofreading.

  View details for DOI 10.1038/nsmb831

  View details for PubMedID 15448679

• Precision Feshbach spectroscopy of ultracold Cs-2 PHYSICAL REVIEW A Chin, C., Vuletic, V., Kerman, A. J., Chu, S., Tiesinga, E., Leo, P. J., Williams, C. J. 2004; 70 (3)

  View details for DOI 10.1103/PhysRevA.70.032701

  View details for Web of Science ID 000224623000070

• tRNA dynamics on the ribosome during translation PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Blanchard, S. C., Kim, H. D., Gonzalez, R. L., Puglisi, J. D., Chu, S. 2004; 101 (35): 12893-12898

  Abstract

  Using single-molecule fluorescence spectroscopy, time-resolved conformational changes between fluorescently labeled tRNA have been characterized within surface-immobilized ribosomes proceeding through a complete cycle of translation elongation. Fluorescence resonance energy transfer was used to observe aminoacyl-tRNA (aa-tRNA) stably accommodating into the aminoacyl site (A site) of the ribosome via a multistep, elongation factor-Tu dependent process. Subsequently, tRNA molecules, bound at the peptidyl site and A site, fluctuate between two configurations assigned as classical and hybrid states. The lifetime of classical and hybrid states, measured for complexes carrying aa-tRNA and peptidyl-tRNA at the A site, shows that peptide bond formation decreases the lifetime of the classical-state tRNA configuration by approximately 6-fold. These data suggest that the growing peptide chain plays a role in modulating fluctuations between hybrid and classical states. Single-molecule fluorescence resonance energy transfer was also used to observe aa-tRNA accommodation coupled with elongation factor G-mediated translocation. Dynamic rearrangements in tRNA configuration are also observed subsequent to the translocation reaction. This work underscores the importance of dynamics in ribosome function and demonstrates single-particle enzymology in a system of more than two components.

  View details for DOI 10.1073/pnas.0403884101

  View details for PubMedID 15317937

• Risk factors for proximal humerus fracture AMERICAN JOURNAL OF EPIDEMIOLOGY Chu, S. P., Kelsey, J. L., Keegan, T. H., Sternfeld, B., Prill, M., Quesenberry, C. P., Sidney, S. 2004; 160 (4): 360-367

  Abstract

  This case-control study of proximal humerus fracture included 448 incident female and male cases and 2,023 controls aged 45 years or older identified in five Northern California Kaiser Permanente Medical Centers in 1996-2001. Data were collected by using an interviewer-administered questionnaire. Some factors related to low bone mass, including number of fractures since age 45 years and low dietary calcium intake, were associated with increased risks of fracture, and factors thought to protect against bone loss, such as menopausal hormone therapy and calcium carbonate tablet use, were associated with reduced risks. Fall-related risk factors included previous falls, diabetes mellitus, and difficulty walking in dim light. Possible fall-related risk factors suggested for the first time in this study were seizure medication use (adjusted odds ratio (OR) = 2.80, 95% confidence interval (CI): 1.45, 5.42), depression (OR = 1.34, 95% CI: 0.98, 1.84), almost always using a hearing aid (OR = 1.92, 95% CI: 1.12, 3.31 vs. never prescribed), and left-handedness (OR = 2.36, 95% CI: 1.51, 3.68 vs. right-handedness). Difficulty with activities of daily living and lack of physical activity tended to be associated with increased risk. Prevention of falls among frail, osteoporotic persons would likely reduce the frequency of proximal humerus fracture.

  View details for DOI 10.1093/aje/kwh224

  View details for Web of Science ID 000223141400008

  View details for PubMedID 15286021

• Magnetic properties of Sm(CobalFe0.31Zr0.05Cu0.04Bx)(z) alloys and their melt-spun materials (x=0.02-0.04, z=7.5-12) IEEE TRANSACTIONS ON MAGNETICS Huang, M. Q., Turgut, Z., Smith, B. R., Chen, Z. M., Ma, B. M., Chu, S. Y., Laughlin, D. E., Horwath, J. C., Fingers, R. T. 2004; 40 (4): 2934-2936

  View details for DOI 10.1109/TMAG.2004.828998

  View details for Web of Science ID 000223446700308

• Single-molecule studies of SNARE complex assembly reveal parallel and antiparallel configurations PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Weninger, K., Bowen, M. E., Chu, S., Brunger, A. T. 2003; 100 (25): 14800-14805

  Abstract

  Vesicle fusion in eukaryotes is thought to involve the assembly of a highly conserved family of proteins termed soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) into a highly stable parallel four-helix bundle. We have used intermolecular single-molecule fluorescence resonance energy transfer to characterize preassembled neuronal SNARE complexes consisting of syntaxin, synaptobrevin, and synaptosome-associated protein of 25 kDa on deposited lipid bilayers. Surprisingly, we found a mixture of parallel as well as antiparallel configurations involving the SNARE motifs of syntaxin and synaptobrevin as well as those of syntaxin and synaptosome-associated protein of 25 kDa. The subpopulation with the parallel four-helix bundle configuration could be greatly enriched by an additional purification step in the presence of denaturant, indicating that the parallel configuration is the energetically most favorable state. Interconversion between the configurations was not observed. From this observation, we infer the conversion rate to be <1.5 h-1. The existence of antiparallel configurations suggests a regulatory role of chaperones, such as N-ethylmaleimide-sensitive factor, or the membrane environment during SNARE complex assembly in vivo, and it could be a partial explanation for the relatively slow rates of vesicle fusion observed by reconstituted fusion experiments in vitro.

  View details for DOI 10.1073/pnas.2036428100

  View details for Web of Science ID 000187227200037

  View details for PubMedID 14657376

  View details for PubMedCentralID PMC299806

• Observation of polymer conformation hysteresis in extensional flow SCIENCE Schroeder, C. M., Babcock, H. P., Shaqfeh, E. S., Chu, S. 2003; 301 (5639): 1515-1519

  Abstract

  Highly extensible Escherichia coli DNA molecules in planar extensional flow were visualized in dilute solution by fluorescence microscopy. For a narrow range of flow strengths, the molecules were found in either a coiled or highly extended conformation, depending on the deformation history of the polymer. This conformation hysteresis persists for many polymer relaxation times and is due to conformation-dependent hydrodynamic forces. Polymer conformational free-energy landscapes were calculated from computer simulations and show two free-energy minima for flow strengths near the coil-stretch transition. Hysteresis cycles may directly influence bulk-solution stresses and the development of stress-strain relations for dilute polymer flows.

  View details for Web of Science ID 000185255300044

  View details for PubMedID 12970560

• Visualization of molecular fluctuations near the critical point of the coil-stretch transition in polymer elongation MACROMOLECULES Babcock, H. P., Teixeira, R. E., Hur, J. S., Shaqfeh, E. S., Chu, S. 2003; 36 (12): 4544-4548

  View details for DOI 10.1021/ma034073p

  View details for Web of Science ID 000183526900041

• Exploration of the transition state for tertiary structure formation between an RNA helix and a large structured RNA JOURNAL OF MOLECULAR BIOLOGY Bartley, L. E., Zhuang, X. W., Das, R., Chu, S., Herschlag, D. 2003; 328 (5): 1011-1026

  Abstract

  Docking of the P1 duplex into the pre-folded core of the Tetrahymena group I ribozyme exemplifies the formation of tertiary interactions in the context of a complex, structured RNA. We have applied Phi-analysis to P1 docking, which compares the effects of modifications on the rate constant for docking (k(dock)) with the effects on the docking equilibrium (K(dock)). To accomplish this we used a single molecule fluorescence resonance energy transfer assay that allows direct determination of the rate constants for formation of thermodynamically favorable, as well as unfavorable, states. Modification of the eight groups of the P1 duplex that make tertiary interactions with the core and changes in solution conditions decrease K(dock) up to 500-fold, whereas k(dock) changes by

  View details for Web of Science ID 000182767000004

  View details for PubMedID 12729738

• Biology and polymer physics at the single-molecule level Meeting on Slow Dynamics in Soft Matter Chu, S. ROYAL SOC. 2003: 689–98

  Abstract

  The ability to look at individual molecules has given us new insights into molecular processes. Examples of our recent work are given to illustrate how behaviour that may otherwise be hidden from view can be clearly seen in single-molecule experiments.

  View details for DOI 10.1098/rsta.2002.1157

  View details for Web of Science ID 000182399900010

  View details for PubMedID 12871618

• Sensitive detection of cold cesium molecules formed on Feshbach resonances PHYSICAL REVIEW LETTERS Chin, C., Kerman, A. J., Vuletic, V., Chu, S. 2003; 90 (3)

  Abstract

  We observe the dynamic formation of quasibound Cs2 molecules near Feshbach resonances in a cold sample of atomic cesium. Using an external probe beam, more than 15 weakly coupled molecular states are detected with high sensitivity, whose collisional formation cross sections are as small as sigma=2 x 10(-16) cm(2). By modeling the molecule formation and dissociation processes with rate equations, we conclude that at an atomic density of 10(13) cm(-3) and temperature of 5 microK, more than 5(1)x10(5) Cs2 molecules in a single rovibrational state coexist with 10(8) Cs atoms in our trap.

  View details for DOI 10.1103/PhysRevLett.90.033201

  View details for Web of Science ID 000180579200015

  View details for PubMedID 12570487

• Early steps of supported bilayer formation probed by single vesicle fluorescence assays BIOPHYSICAL JOURNAL Johnson, J. M., Ha, T., Chu, S., Boxer, S. G. 2002; 83 (6): 3371-3379

  Abstract

  We have developed a single vesicle assay to study the mechanisms of supported bilayer formation. Fluorescently labeled, unilamellar vesicles (30-100 nm diameter) were first adsorbed to a quartz surface at low enough surface concentrations to visualize single vesicles. Fusion and rupture events during the bilayer formation, induced by the subsequent addition of unlabeled vesicles, were detected by measuring two-color fluorescence signals simultaneously. Lipid-conjugated dyes monitored the membrane fusion while encapsulated dyes reported on the vesicle rupture. Four dominant pathways were observed, each exhibiting characteristic two-color fluorescence signatures: 1) primary fusion, in which an unlabeled vesicle fuses with a labeled vesicle on the surface, is signified by the dequenching of the lipid-conjugated dyes followed by rupture and final merging into the bilayer; 2) simultaneous fusion and rupture, in which a labeled vesicle on the surface ruptures simultaneously upon fusion with an unlabeled vesicle; 3) no dequenching, in which loss of fluorescence signal from both dyes occur simultaneously with the final merger into the bilayer; and 4) isolated rupture (pre-ruptured vesicles), in which a labeled vesicle on the surface spontaneously undergoes content loss, a process that occurs with high efficiency in the presence of a high concentration of Texas Red-labeled lipids. Vesicles that have undergone content loss appear to be more fusogenic than intact vesicles.

  View details for Web of Science ID 000180256300040

  View details for PubMedID 12496104

• Dynamics and configurational fluctuations of single DNA molecules in linear mixed flows PHYSICAL REVIEW E Hur, J. S., Shaqfeh, E. S., Babcock, H. P., Chu, S. 2002; 66 (1)

  Abstract

  We examine the dynamics of DNA molecules in mixed flows where the ratio of vorticity to strain rate may be slightly above or below unity via Brownian dynamics simulation. We find that the chain dynamics in these flows are dramatically different than those found for simple shear flow. When the strain rate exceeds vorticity, the dynamics are found to be driven by the extra amount of straining. For vorticity-dominated flows, a periodicity in chain extension is observed with considerable chain deformation.

  View details for DOI 10.1103/PhysRevE.66.011915

  View details for Web of Science ID 000177200500061

  View details for PubMedID 12241392

• Correlating structural dynamics and function in single ribozyme molecules SCIENCE Zhuang, X. W., Kim, H., Pereira, M. J., Babcock, H. P., Walter, N. G., Chu, S. 2002; 296 (5572): 1473-1476

  Abstract

  We have studied the correlation between structural dynamics and function of the hairpin ribozyme. The enzyme-substrate complex exists in either docked (active) or undocked (inactive) conformations. Using single-molecule fluorescence methods, we found complex structural dynamics with four docked states of distinct stabilities and a strong memory effect where each molecule rarely switches between different docked states. We also found substrate cleavage to be rate-limited by a combination of conformational transitions and reversible chemistry equilibrium. The complex structural dynamics quantitatively explain the heterogeneous cleavage kinetics common to many catalytic RNAs. The intimate coupling of structural dynamics and function is likely a general phenomenon for RNA.

  View details for Web of Science ID 000175910300050

  View details for PubMedID 12029135

• Mg2+-dependent conformational change of RNA studied by fluorescence correlation and FRET on immobilized single molecules PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Kim, H. D., Nienhaus, G. U., Ha, T., Orr, J. W., Williamson, J. R., Chu, S. 2002; 99 (7): 4284-4289

  Abstract

  Fluorescence correlation spectroscopy (FCS) of fluorescence resonant energy transfer (FRET) on immobilized individual fluorophores was used to study the Mg2+-facilitated conformational change of an RNA three-helix junction, a structural element that initiates the folding of the 30S ribosomal subunit. Transitions of the RNA junction between open and folded conformations resulted in fluctuations in fluorescence by FRET. Fluorescence fluctuations occurring between two FRET states on the millisecond time scale were found to be dependent on Mg2+ and Na+ concentrations. Correlation functions of the fluctuations were used to determine transition rates between the two conformations as a function of Mg2+ or Na+ concentration. Both the opening and folding rates were found to vary with changing salt conditions. Assuming specific binding of divalent ions to RNA, the Mg2+ dependence of the observed rates cannot be explained by conformational change induced by Mg2+ binding/unbinding, but is consistent with a model in which the intrinsic conformational change of the RNA junction is altered by uptake of Mg2+ ion(s). This version of FCS/FRET on immobilized single molecules is demonstrated to be a powerful technique in the study of conformational dynamics of biomolecules over time scales ranging from microseconds to seconds.

  View details for Web of Science ID 000174856000030

  View details for PubMedID 11929999

• Cold atoms and quantum control NATURE Chu, S. 2002; 416 (6877): 206-210

  Abstract

  This overview prefaces a collection of Insight review articles on the physics and applications of laser-cooled atoms. I will cast this work into a historical perspective in which laser cooling and trapping is seen as one of several research directions aimed at controlling the internal and external degrees of freedom of atoms and molecules.

  View details for Web of Science ID 000174348100046

  View details for PubMedID 11894103

• Exploring the folding landscape of a structured RNA PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Russell, R., Zhuang, X. W., Babcock, H. P., Millett, I. S., Doniach, S., Chu, S., Herschlag, D. 2002; 99 (1): 155-160

  Abstract

  Structured RNAs achieve their active states by traversing complex, multidimensional energetic landscapes. Here we probe the folding landscape of the Tetrahymena ribozyme by using a powerful approach: the folding of single ribozyme molecules is followed beginning from distinct regions of the folding landscape. The experiments, combined with small-angle x-ray scattering results, show that the landscape contains discrete folding pathways. These pathways are separated by large free-energy barriers that prevent interconversion between them, indicating that the pathways lie in deep channels in the folding landscape. Chemical protection and mutagenesis experiments are then used to elucidate the structural features that determine which folding pathway is followed. Strikingly, a specific long-range tertiary contact can either help folding or hinder folding, depending on when it is formed during the process. Together these results provide an unprecedented view of the topology of an RNA folding landscape and the RNA structural features that underlie this multidimensional landscape.

  View details for Web of Science ID 000173233300031

  View details for PubMedID 11756689

• Measurement of an electron's electric dipole moment using Cs atoms trapped in optical lattices PHYSICAL REVIEW A Chin, C., Leiber, V., Vuletic, V., Kerman, A. J., Chu, S. 2001; 63 (3)

  View details for Web of Science ID 000167321000079

• Dynamics of dilute and semidilute DNA solutions in the start-up of shear flow JOURNAL OF RHEOLOGY Hur, J. S., Shaqfeh, E. S., Babcock, H. P., Smith, D. E., Chu, S. 2001; 45 (2): 421-450

  View details for Web of Science ID 000167378100007

• A single molecule study of a multiple-step RNA enzymatic reaction Zhuang, X. W., Kim, H., Walter, N., Babcock, H., Chu, S. BIOPHYSICAL SOCIETY. 2001: 157A

  View details for Web of Science ID 000166692200725

• Initial steps of bilayer formation investigated using single vesicle fluorescence. Johnson, J. M., Ha, T. J., Chu, S., Boxer, S. G. BIOPHYSICAL SOCIETY. 2001: 417A

  View details for Web of Science ID 000166692201900

• Fluorescence quenching: A tool for single-molecule protein-folding study PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Zhuang, X. W., Ha, T., Kim, H. D., Centner, T., Labeit, S., Chu, S. 2000; 97 (26): 14241-14244

  Abstract

  By using titin as a model system, we have demonstrated that fluorescence quenching can be used to study protein folding at the single molecule level. The unfolded titin molecules with multiple dye molecules attached are able to fold to the native state. In the native folded state, the fluorescence from dye molecules is quenched due to the close proximity between the dye molecules. Unfolding of the titin leads to a dramatic increase in the fluorescence intensity. Such a change makes the folded and unfolded states of a single titin molecule clearly distinguishable and allows us to measure the folding dynamics of individual titin molecules in real time. We have also shown that fluorescence quenching can signal folding and unfolding of a small protein with only one immunoglobulin domain.

  View details for Web of Science ID 000165993700047

  View details for PubMedID 11121030

• High resolution feshbach spectroscopy of cesium Physical review letters Chin, C., Vuletic, V., Kerman, A. J., Chu, S. 2000; 85 (13): 2717-20

  Abstract

  We measure high-resolution Feshbach resonance spectra for ultracold cesium atoms colliding in different hyperfine and magnetic sublevels. More than 25 resonances are observed for magnetic fields up to 230 G and their positions are measured with an accuracy down to 0.03 G. From these spectra several ground-state molecular interaction parameters can be extracted with sufficient accuracy to permit for the first time an unambiguous and accurate determination of cesium's ultracold collision properties [P. J. Leo, C. J. Williams, and P. S. Julienne, following Letter, Phys. Rev. Lett. 85, 2721 (2000)].

  View details for PubMedID 10991216

• High resolution Feshbach spectroscopy of cesium PHYSICAL REVIEW LETTERS Chin, C., Vuletic, V., Kerman, A. J., Chu, S. 2000; 85 (13): 2717-2720

  View details for Web of Science ID 000089465100016

• Relating the microscopic and macroscopic response of a polymeric fluid in a shearing flow PHYSICAL REVIEW LETTERS Babcock, H. P., Smith, D. E., Hur, J. S., Shaqfeh, E. S., Chu, S. 2000; 85 (9): 2018-2021

  Abstract

  The microscopic and macroscopic response of a polymer solution in start-up shear flow was investigated using fluorescence microscopy of single molecules, bulk viscosity measurements, and Brownian dynamics simulations. An overshoot in viscosity was observed upon flow inception and understood via the observed molecular extension and by simulation findings. Increasing the polymer concentration up to six times the overlap concentration ( C(*)) has no effect on the character of the dynamics of individual molecules.

  View details for Web of Science ID 000088965300060

  View details for PubMedID 10970672

• A single-molecule study of RNA catalysis and folding SCIENCE Zhuang, X. W., Bartley, L. E., Babcock, H. P., Russell, R., Ha, T. J., Herschlag, D., Chu, S. 2000; 288 (5473): 2048-?

  Abstract

  Using fluorescence microscopy, we studied the catalysis by and folding of individual Tetrahymena thermophila ribozyme molecules. The dye-labeled and surface-immobilized ribozymes used were shown to be functionally indistinguishable from the unmodified free ribozyme in solution. A reversible local folding step in which a duplex docks and undocks from the ribozyme core was observed directly in single-molecule time trajectories, allowing the determination of the rate constants and characterization of the transition state. A rarely populated docked state, not measurable by ensemble methods, was observed. In the overall folding process, intermediate folding states and multiple folding pathways were observed. In addition to observing previously established folding pathways, a pathway with an observed folding rate constant of 1 per second was discovered. These results establish single-molecule fluorescence as a powerful tool for examining RNA folding.

  View details for Web of Science ID 000087687000052

  View details for PubMedID 10856219

• Laser cooling of atoms, ions, or molecules by coherent scattering Physical review letters Vuletic, V., Chu, S. 2000; 84 (17): 3787-90

  Abstract

  We point out a laser cooling method for atoms, molecules, or ions at low saturation and large detuning from the particles' resonances. The moving particle modifies the field inside a cavity with a time delay characteristic of the cavity linewidth, while the field acts on the particle via the light shift. The dissipative mechanism can be interpreted as Doppler cooling based on preferential scattering rather than preferential absorption. It depends on particle properties only through the coherent scattering rate, opening new possibilities for optically cooling molecules or interacting atoms.

  View details for PubMedID 11019206

• Laser cooling of atoms, ions, or molecules by coherent scattering PHYSICAL REVIEW LETTERS Vuletic, V., Chu, S. 2000; 84 (17): 3787-3790

  View details for Web of Science ID 000086635900014

• Beyond optical molasses: 3D raman sideband cooling of atomic cesium to high phase-space density Physical review letters Kerman, A. J., Vuletic, V., Chin, C., Chu, S. 2000; 84 (3): 439-42

  Abstract

  We demonstrate a simple, general purpose method to cool neutral atoms. A sample containing 3x10(8) cesium atoms prepared in a magneto-optical trap is cooled and simultaneously spin polarized in 10 ms at a density of 1.1x10(11) cm (-3) to a phase space density nlambda(3)(dB) = 1/500, which is almost 3 orders of magnitude higher than attainable in free space with optical molasses. The technique is based on 3D degenerate Raman sideband cooling in optical lattices and remains efficient even at densities where the mean lattice site occupation is close to unity.

  View details for PubMedID 11015933

• Beyond optical molasses: 3D Raman sideband cooling of atomic cesium to high phase-space density PHYSICAL REVIEW LETTERS Kerman, A. J., Vuletic, V., Chin, C., Chu, S. 2000; 84 (3): 439-442

  View details for Web of Science ID 000084787300011

• Ligand-induced conformational changes observed in single RNA molecules PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Ha, T., Zhuang, X. W., Kim, H. D., Orr, J. W., Williamson, J. R., Chu, S. 1999; 96 (16): 9077-9082

  Abstract

  We present the first demonstration that fluorescence resonance energy transfer can be used to track the motion of a single molecule undergoing conformational changes. As a model system, the conformational changes of individual three-helix junction RNA molecules induced by the binding of ribosomal protein S15 or Mg(2+) ions were studied by changes in single-molecule fluorescence. The transition from an open to a folded configuration was monitored by the change of fluorescence resonance energy transfer between two different dye molecules attached to the ends of two helices in the RNA junction. Averaged behavior of RNA molecules closely resembles that of unlabeled molecules in solution determined by other bulk assays, proving that this approach is viable and suggesting new opportunities for studying protein-nucleic acids interactions. Surprisingly, we observed an anomalously broad distribution of RNA conformations at intermediate ion concentrations that may be attributed to foldability differences among RNA molecules. In addition, an experimental scheme was developed where the real-time response of single molecules can be followed under changing environments. As a demonstration, we repeatedly changed Mg(2+) concentration in the buffer while monitoring single RNA molecules and showed that individual RNA molecules can measure the instantaneous Mg(2+) concentration with 20-ms time resolution, making it the world's smallest Mg(2+) meter.

  View details for Web of Science ID 000081835500056

  View details for PubMedID 10430898

• Suppression of atomic radiative collisions by tuning the ground state scattering length PHYSICAL REVIEW LETTERS Vuletic, V., Chin, C., Kerman, A. J., Chu, S. 1999; 83 (5): 943-946

  View details for Web of Science ID 000081820400014

• Active low frequency vertical vibration isolation REVIEW OF SCIENTIFIC INSTRUMENTS Hensley, J. M., Peters, A., Chu, S. 1999; 70 (6): 2735-2741

  View details for Web of Science ID 000080613500025

• Single-polymer dynamics in steady shear flow SCIENCE Smith, D. E., Babcock, H. P., Chu, S. 1999; 283 (5408): 1724-1727

  Abstract

  The conformational dynamics of individual, flexible polymers in steady shear flow were directly observed by the use of video fluorescence microscopy. The probability distribution for the molecular extension was determined as a function of shear rate, gamma;, for two different polymer relaxation times, tau. In contrast to the behavior in pure elongational flow, the average polymer extension in shear flow does not display a sharp coil-stretch transition. Large, aperiodic temporal fluctuations were observed, consistent with end-over-end tumbling of the molecule. The rate of these fluctuations (relative to the relaxation rate) increased as the Weissenberg number, gamma;tau, was increased.

  View details for Web of Science ID 000079102800048

  View details for PubMedID 10073935

• Brownian dynamics simulations of a DNA molecule in an extensional flow field JOURNAL OF RHEOLOGY Larson, R. G., Hu, H., Smith, D. E., Chu, S. 1999; 43 (2): 267-304

  View details for Web of Science ID 000078965200001

• Observation of low-field Feshbach resonances in collisions of cesium atoms PHYSICAL REVIEW LETTERS Vuletic, V., Kerman, A. J., Chin, C., Chu, S. 1999; 82 (7): 1406-1409

  View details for Web of Science ID 000078623500016

• Degenerate Raman sideband cooling of trapped cesium atoms at very high atomic densities PHYSICAL REVIEW LETTERS Vuletic, V., Chin, C., Kerman, A. J., Chu, S. 1998; 81 (26): 5768-5771

  View details for Web of Science ID 000077760200015

• Response of flexible polymers to a sudden elongational flow Science (New York, N.Y.) Smith, D. E., Chu, S. 1998; 281 (5381): 1335-40

  Abstract

  Individual polymers at thermal equilibrium were exposed to an elongational flow producing a high strain rate, and their dynamics were recorded with video fluorescence microscopy. The flow was turned on suddenly so that the entire evolution of molecular conformation could be observed without initial perturbations. The rate of stretching of individual molecules is highly variable and depends on the molecular conformation that develops during stretching. This variability is due to a dependence of the dynamics on the initial, random equilibrium conformation of the polymer coil. The increasing appearance at high strain rates of slowly unraveling hairpin folds is an example of nonergodic dynamics, which can occur when a statistical mechanical system is subjected to nonadiabatic, or "sudden," external forces.

  View details for PubMedID 9721095

• The dynamics of partially extended single molecules of DNA NATURE Quake, S. R., Babcock, H., Chu, S. 1997; 388 (6638): 151-154

  Abstract

  The behaviour of an isolated polymer floating in a solvent forms the basis of our understanding of polymer dynamics. Classical theories describe the motion of a polymer with linear equations of motion, which yield a set of 'normal modes', analogous to the fundamental frequency and the harmonics of a vibrating violin string. But hydrodynamic interactions make polymer dynamics inherently nonlinear, and the linearizing approximations required for the normal-mode picture have therefore been questioned. Here we test the normal-mode theory by measuring the fluctuations of single molecules of DNA held in a partially extended state with optical tweezers. We find that the motion of the DNA can be described by linearly independent normal modes, and we have experimentally determined the eigenstates of the system. Furthermore, we show that the spectrum of relaxation times obeys a power law.

  View details for Web of Science ID A1997XK10900043

  View details for PubMedID 9217154

• Single polymer dynamics in an elongational flow SCIENCE Perkins, T. T., Smith, D. E., Chu, S. 1997; 276 (5321): 2016-2021

  Abstract

  The stretching of individual polymers in a spatially homogeneous velocity gradient was observed through use of fluorescently labeled DNA molecules. The probability distribution of molecular extension was determined as a function of time and strain rate. Although some molecules reached steady state, the average extension did not, even after a approximately 300-fold distortion of the underlying fluid element. At the highest strain rates, distinct conformational shapes with differing dynamics were observed. There was considerable variation in the onset of stretching, and chains with a dumbbell shape stretched more rapidly than folded ones. As the strain rate was increased, chains did not deform with the fluid element. The steady-state extension can be described by a model consisting of two beads connected by a spring representing the entropic elasticity of a worm-like chain, but the average dynamics cannot.

  View details for Web of Science ID A1997XG74800057

  View details for PubMedID 9197259

• Bioreactive self-assembled monolayers on hydrogen-passivated Si(111) as a new class of atomically flat substrates for biological scanning probe microscopy JOURNAL OF STRUCTURAL BIOLOGY Wagner, P., Nock, S., Spudich, J. A., VOLKMUTH, W. D., Chu, S., Cicero, R. L., Wade, C. P., Linford, M. R., Chidsey, C. E. 1997; 119 (2): 189-201

  Abstract

  This is the first report of bioreactive self-assembled monolayers, covalently bound to atomically flat silicon surfaces and capable of binding biomolecules for investigation by scanning probe microscopy and other surface-related assays and sensing devices. These monolayers are stable under a wide range of conditions and allow tailor-made functionalization for many purposes. We describe the substrate preparation and present an STM and SFM characterization, partly performed with multiwalled carbon nanotubes as tapping-mode supertips. Furthermore, we present two strategies of introducing in situ reactive headgroup functionalities. One method entails a free radical chlorosulfonation process with subsequent sulfonamide formation. A second method employs singlet carbenemediated hydrogen-carbon insertion of a heterobifunctional, amino-reactive trifluoromethyl-diazirinyl crosslinker. We believe that this new substrate is advantageous to others, because it (i) is atomically flat over large areas and can be prepared in a few hours with standard equipment, (ii) is stable under most conditions, (iii) can be modified to adjust a certain degree of reactivity and hydrophobicity, which allows physical adsorption or covalent crosslinking of the biological specimen, (iv) builds the bridge between semiconductor microfabrication and organic/biological molecular systems, and (v) is accessible to nanopatterning and applications requiring conductive substrates.

  View details for Web of Science ID A1997XN38200014

  View details for PubMedID 9245759

• Raman cooling of atoms in an optical dipole trap PHYSICAL REVIEW LETTERS Lee, H. J., Adams, C. S., Kasevich, M., Chu, S. 1996; 76 (15): 2658-2661

  View details for Web of Science ID A1996UE19000014

• Quantitative measurements of force and displacement using an optical trap BIOPHYSICAL JOURNAL Simmons, R. M., Finer, J. T., Chu, S., Spudich, J. A. 1996; 70 (4): 1813-1822

  Abstract

  We combined a single-beam gradient optical trap with a high-resolution photodiode position detector to show that an optical trap can be used to make quantitative measurements of nanometer displacements and piconewton forces with millisecond resolution. When an external force is applied to a micron-sized bead held by an optical trap, the bead is displaced from the center of the trap by an amount proportional to the applied force. When the applied force is changed rapidly, the rise time of the displacement is on the millisecond time scale, and thus a trapped bead can be used as a force transducer. The performance can be enhanced by a feedback circuit so that the position of the trap moves by means of acousto-optic modulators to exert a force equal and opposite to the external force applied to the bead. In this case the position of the trap can be used to measure the applied force. We consider parameters of the trapped bead such as stiffness and response time as a function of bead diameter and laser beam power and compare the results with recent ray-optic calculations.

  View details for Web of Science ID A1996UB81800027

  View details for PubMedID 8785341

  View details for PubMedCentralID PMC1225151

• Dynamical scaling of DNA diffusion coefficients MACROMOLECULES Smith, D. E., Perkins, T. T., Chu, S. 1996; 29 (4): 1372-1373

  View details for Web of Science ID A1996TV62000043

• EVAPORATIVE COOLING IN A CROSSED DIPOLE TRAP PHYSICAL REVIEW LETTERS Adams, C. S., Lee, H. J., Davidson, N., Kasevich, M., Chu, S. 1995; 74 (18): 3577-3580

  View details for Web of Science ID A1995QV14900019

• STRETCHING OF A SINGLE TETHERED POLYMER IN A UNIFORM-FLOW SCIENCE Perkins, T. T., Smith, D. E., Larson, R. G., Chu, S. 1995; 268 (5207): 83-87

  Abstract

  The stretching of single, tethered DNA molecules by a flow was directly visualized with fluorescence microscopy. Molecules ranging in length (L) from 22 to 84 micrometers were held stationary against the flow by the optical trapping of a latex microsphere attached to one end. The fractional extension x/L is a universal function of eta vL 0.54 +/- 0.05, where eta and v are the viscosity and velocity of the flow, respectively. This relation shows that the DNA is not "free-draining" (that is, hydrodynamic coupling within the chain is not negligible) even near full extension (approximately 80 percent). This function has the same form over a long range as the fractional extension versus force applied at the ends of a worm-like chain. For small deformations (< 30 percent of full extension), the extension increases with velocity as x approximately v0.70 +/- 0.08. The relative size of fluctuations in extension decreases as sigma x/x approximately equal to 0.42 exp (-4.9 x/L). Video images of the fluctuating chain have a cone-like envelope and show a sharp increase in intensity at the free end.

  View details for Web of Science ID A1995QR45400029

  View details for PubMedID 7701345

• LONG ATOMIC COHERENCE TIMES IN AN OPTICAL DIPOLE TRAP PHYSICAL REVIEW LETTERS Davidson, N., Lee, H. J., Adams, C. S., Kasevich, M., Chu, S. 1995; 74 (8): 1311-1314

  View details for Web of Science ID A1995QH29300014

• RAMAN COOLING OF ATOMS IN 2-DIMENSIONS AND 3-DIMENSIONS PHYSICAL REVIEW LETTERS Davidson, N., Lee, H. J., Kasevich, M., Chu, S. 1994; 72 (20): 3158-3161

  View details for Web of Science ID A1994NL60900007

• RELAXATION OF A SINGLE DNA MOLECULE OBSERVED BY OPTICAL MICROSCOPY SCIENCE Perkins, T. T., Quake, S. R., Smith, D. E., Chu, S. 1994; 264 (5160): 822-826

  Abstract

  Single molecules of DNA, visualized in video fluorescence microscopy, were stretched to full extension in a flow, and their relaxation was measured when the flow stopped. The molecules, attached by one end to a 1-micrometer bead, were manipulated in an aqueous solution with optical tweezers. Inverse Laplace transformations of the relaxation data yielded spectra of decaying exponentials with distinct peaks, and the longest time component (tau) increased with length (L) as tau approximately L 1.68 +/- 0.10. A rescaling analysis showed that most of the relaxation curves had a universal shape and their characteristic times (lambda t) increased as lambda t approximately L 1.65 +/- 0.13. These results are in qualitative agreement with the theoretical prediction of dynamical scaling.

  View details for Web of Science ID A1994NJ94900026

  View details for PubMedID 8171336

• DIRECT OBSERVATION OF TUBE-LIKE MOTION OF A SINGLE POLYMER-CHAIN SCIENCE Perkins, T. T., Smith, D. E., Chu, S. 1994; 264 (5160): 819-822

  Abstract

  Tube-like motion of a single, fluorescently labeled molecule of DNA in an entangled solution of unlabeled lambda-phage DNA molecules was observed by fluorescence microscopy. One end of a 16- to 100-micrometer-long DNA was attached to a 1-micrometer bead and moved with optical tweezers. The molecule was stretched into various conformations having bends, kinks, and loops. As the polymer relaxed, it closely followed a path defined by its initial contour. The relaxation time of the disturbance caused by the bead was roughly 1 second, whereas tube-like motion in small loops persisted for longer than 2 minutes. Tube deformation, constraint release, and excess chain segment diffusion were also observed. These observations provide direct evidence for several key assumptions in the reptation model developed by de Gennes, Edwards, and Doi.

  View details for Web of Science ID A1994NJ94900025

  View details for PubMedID 8171335

• PRECISION ATOM INTERFEROMETRY AND AN IMPROVED MEASUREMENT OF THE 13S1-23S1 TRANSITION IN POSITRONIUM International School of Physics - Enrico Fermi Chu, S. ELSEVIER SCIENCE PUBL B V. 1994: 317–355

  View details for Web of Science ID A1994BC24Y00014

• PRECISION-MEASUREMENTS WITH COLD ATOMS 11th International Conference on Laser Spectroscopy Weiss, D. S., Gibble, K., Young, B., Peters, A., Chu, S. AIP PRESS. 1994: 23–28

  View details for Web of Science ID A1994BA06J00005

• LASER-COOLED CS FREQUENCY STANDARD AND A MEASUREMENT OF THE FREQUENCY-SHIFT DUE TO ULTRACOLD COLLISIONS PHYSICAL REVIEW LETTERS Gibble, K., Chu, S. 1993; 70 (12): 1771-1774

  View details for Web of Science ID A1993KT36700010

• IN-VITRO METHODS FOR MEASURING FORCE AND VELOCITY OF THE ACTIN-MYOSIN INTERACTION USING PURIFIED PROTEINS METHODS IN CELL BIOLOGY, VOL 39 Warrick, H. M., Simmons, R. M., Finer, J. T., Uyeda, T. Q., Chu, S., Spudich, J. A. 1993; 39: 1-21

  View details for Web of Science ID A1993BZ58U00001

  View details for PubMedID 8246790

• LASER COOLING BELOW A PHOTON RECOIL WITH 3-LEVEL ATOMS PHYSICAL REVIEW LETTERS Kasevich, M., Chu, S. 1992; 69 (12): 1741-1744

  View details for Web of Science ID A1992JN94600007

• MEASUREMENT OF THE GRAVITATIONAL ACCELERATION OF AN ATOM WITH A LIGHT-PULSE ATOM INTERFEROMETER APPLIED PHYSICS B-PHOTOPHYSICS AND LASER CHEMISTRY Kasevich, M., Chu, S. 1992; 54 (5): 321-332

  View details for Web of Science ID A1992HV50800002

• FUTURE SLOW-ATOM FREQUENCY STANDARDS METROLOGIA Gibble, K., Chu, S. 1992; 29 (2): 201-212

  View details for Web of Science ID A1992JH32800008

• IMPROVED MAGNETOOPTIC TRAPPING IN A VAPOR CELL OPTICS LETTERS GIBBLE, K. E., Kasapi, S., Chu, S. 1992; 17 (7): 526-528

  Abstract

  We have captured 3.6 x 10(10) cesium atoms in a magneto-optic trap loaded from a vapor cell. The 300-fold increase in the number of trapped atoms compared with that of previous research was accomplished by using larger laser intensities and 4-cm-diameter laser beams. The loading time constant was as short as 0.2 s.

  View details for Web of Science ID A1992HK74400022

  View details for PubMedID 19794547

• LASER TRAPPING OF NEUTRAL PARTICLES SCIENTIFIC AMERICAN Chu, S. 1992; 266 (2): 70-76

  View details for Web of Science ID A1992HA26000012

• MEASUREMENT OF THE ACCELERATION DUE TO GRAVITY WITH AN ATOMIC INTERFEROMETER WORKSHOP ON THE FOUNDATIONS OF QUANTUM MECHANICS Kasevich, M., Chu, S. WORLD SCIENTIFIC PUBL CO PTE LTD. 1992: 47–54

  View details for Web of Science ID A1992BW53X00005

• THEORETICAL-ANALYSIS OF VELOCITY-SELECTIVE RAMAN TRANSITIONS PHYSICAL REVIEW A Moler, K., Weiss, D. S., Kasevich, M., Chu, S. 1992; 45 (1): 342-348

  View details for Web of Science ID A1992GY51800046

• ATOMIC INTERFEROMETRY USING STIMULATED RAMAN TRANSITIONS PHYSICAL REVIEW LETTERS Kasevich, M., Chu, S. 1991; 67 (2): 181-184

  View details for Web of Science ID A1991FV18200006

• ATOMIC VELOCITY SELECTION USING STIMULATED RAMAN TRANSITIONS PHYSICAL REVIEW LETTERS Kasevich, M., Weiss, D. S., Riis, E., Moler, K., Kasapi, S., Chu, S. 1991; 66 (18): 2297-2300

  View details for Web of Science ID A1991FK18300005

• NORMAL-INCIDENCE REFLECTION OF SLOW ATOMS FROM AN OPTICAL EVANESCENT WAVE OPTICS LETTERS Kasevich, M. A., Weiss, D. S., Chu, S. 1990; 15 (11): 607-609

  View details for Web of Science ID A1990DG12400005

  View details for PubMedID 19768022

• ATOM FUNNEL FOR THE PRODUCTION OF A SLOW, HIGH-DENSITY ATOMIC-BEAM PHYSICAL REVIEW LETTERS Riis, E., Weiss, D. S., Moler, K. A., Chu, S. 1990; 64 (14): 1658-1661

  View details for Web of Science ID A1990CW76100014

• OPTICAL MOLASSES AND MULTILEVEL ATOMS - THEORY JOURNAL OF THE OPTICAL SOCIETY OF AMERICA B-OPTICAL PHYSICS UNGAR, P. J., Weiss, D. S., Riis, E., Chu, S. 1989; 6 (11): 2058-2071

  View details for Web of Science ID A1989AZ11500014

• OPTICAL MOLASSES AND MULTILEVEL ATOMS - EXPERIMENT JOURNAL OF THE OPTICAL SOCIETY OF AMERICA B-OPTICAL PHYSICS Weiss, D. S., Riis, E., Shevy, Y., UNGAR, P. J., Chu, S. 1989; 6 (11): 2072-2083

  View details for Web of Science ID A1989AZ11500015

• RF SPECTROSCOPY IN AN ATOMIC FOUNTAIN PHYSICAL REVIEW LETTERS Kasevich, M. A., Riis, E., Chu, S., DeVoe, R. G. 1989; 63 (6): 612-616

  View details for Web of Science ID A1989AJ69400008

• BIMODAL SPEED DISTRIBUTIONS IN LASER-COOLED ATOMS PHYSICAL REVIEW LETTERS Shevy, Y., Weiss, D. S., UNGAR, P. J., Chu, S. 1989; 62 (10): 1118-1121

  View details for Web of Science ID A1989T487800014