Dr. Cui's research interest lies in understanding the signal propagation in neurons using quantitative tools developed by physical and chemical sciences. The problem of interest is on the long-range signal propagation in axons and its implication in neurodegenerative diseases. Methods of interest include single molecule fluorescence imaging, magnetic and optical trapping, photo-lithography, microfluidic neuronal platform, and electrophysiology recording.

Academic Appointments

Honors & Awards

  • NIH Pathway to Independence Career Award, NIH (2006)
  • Dreyfus New Faculty Award, Dreyfus foundation (2008)
  • Searle Scholar Award, Searle (2009)
  • Packard Fellowships for Science and Engineering, Packard Foundation (2009)
  • Hellman Scholar, Hellman Foundation (2011)
  • NSF CAREER award, NSF (2011)
  • NIH New Innovator Award, NIH (2012)
  • NSF INSPIRE award, NSF (2013)

Professional Education

  • Ph.D., University of Chicago, Physical Chemistry (2002)
  • M.S., University of Chicago, Chemistry (2000)
  • B.S., University of Science & Technology of China, Material Sci. & Eng. (1998)

Current Research and Scholarly Interests

We are developing various physical and chemical approaches to study biological processes in neurons. There are three major research directions: (1) Investigating the axonal transport process using optical imging, magnetic and optical trapping, and microfluidic platform; (2) Developing vertical nanopillar-based electric and optic sensors for sensitive detection of biological functions; (3) Using optogentic approach to investigate temporal and spatial control of intracellular signaling pathways.

2015-16 Courses

Stanford Advisees

All Publications

  • Optogenetic control of intracellular signaling pathways TRENDS IN BIOTECHNOLOGY Zhang, K., Cu, B. 2015; 33 (2): 92-100
  • U0126 Protects Cells against Oxidative Stress Independent of Its Function as a MEK Inhibitor ACS CHEMICAL NEUROSCIENCE Ong, Q., Guo, S., Zhang, K., Cui, B. 2015; 6 (1): 130-137


    U0126 is a potent and selective inhibitor of MEK1 and MEK2 kinases. It has been widely used as an inhibitor for the Ras/Raf/MEK/ERK signaling pathway with over 5000 references on the NCBI PubMed database. In particular, U0126 has been used in a number of studies to show that inhibition of the Raf/MEK/ERK pathway protects neuronal cells against oxidative stress. Here, we report that U0126 can function as an antioxidant that protects PC12 cells against a number of different oxidative-stress inducers. This protective effect of U0126 is independent of its function as a MEK inhibitor, as several other MEK inhibitors failed to show similar protective effects. U0126 reduces reactive oxygen species (ROS) in cells. We further demonstrate that U0126 is a direct ROS scavenger in vitro, and the oxidation products of U0126 exhibit fluorescence. Our finding that U0126 is a strong antioxidant signals caution for its future usage as a MEK inhibitor and for interpreting some previous results.

    View details for DOI 10.1021/cn500288n

    View details for Web of Science ID 000348338900016

    View details for PubMedID 25544156

  • Enhancing the Nanomaterial Bio-Interface by Addition of Mesoscale Secondary Features: Crinkling of Carbon Nanotube Films To Create Subcellular Ridges ACS NANO Xie, X., Zhao, W., Lee, H. R., Liu, C., Ye, M., Xie, W., Cui, B., Criddle, C. S., Cui, Y. 2014; 8 (12): 11958-11965


    Biological cells often interact with their local environment through subcellular structures at a scale of tens to hundreds of nanometers. This study investigated whether topographic features fabricated at a similar scale would impact cellular functions by promoting the interaction between subcellular structures and nanomaterials. Crinkling of carbon nanotube films by solvent-induced swelling and shrinkage of substrate resulted in the formation of ridge features at the subcellular scale on both flat and three-dimensional substrates. Biological cells grown upon these crinkled CNT films had enhanced activity: neuronal cells grew to higher density and displayed greater cell polarization; exoelectrogenic micro-organisms transferred electrons more efficiently. The results indicate that crinkling of thin CNT films creates secondary mesoscale features that enhance attachment, growth, and electron transfer.

    View details for DOI 10.1021/nn504898p

    View details for Web of Science ID 000347138000008

  • Chemically defined generation of human cardiomyocytes NATURE METHODS Burridge, P. W., Matsa, E., Shukla, P., Lin, Z. C., Churko, J. M., Ebert, A. D., Lan, F., Diecke, S., Huber, B., Mordwinkin, N. M., Plews, J. R., Abilez, O. J., Cui, B., Gold, J. D., Wu, J. C. 2014; 11 (8): 855-860


    Existing methods for human induced pluripotent stem cell (hiPSC) cardiac differentiation are efficient but require complex, undefined medium constituents that hinder further elucidation of the molecular mechanisms of cardiomyogenesis. Using hiPSCs derived under chemically defined conditions on synthetic matrices, we systematically developed an optimized cardiac differentiation strategy, using a chemically defined medium consisting of just three components: the basal medium RPMI 1640, L-ascorbic acid 2-phosphate and rice-derived recombinant human albumin. Along with small molecule-based induction of differentiation, this protocol produced contractile sheets of up to 95% TNNT2(+) cardiomyocytes at a yield of up to 100 cardiomyocytes for every input pluripotent cell and was effective in 11 hiPSC lines tested. This chemically defined platform for cardiac specification of hiPSCs will allow the elucidation of cardiomyocyte macromolecular and metabolic requirements and will provide a minimal system for the study of maturation and subtype specification.

    View details for DOI 10.1038/NMETH.2999

    View details for Web of Science ID 000340075600026

    View details for PubMedID 24930130

  • Lighting up FGFR signaling. Chemistry & biology Zhang, K., Cui, B. 2014; 21 (7): 806-808


    In this issue of Chemistry & Biology, Kim and colleagues describe their work on optogenetic control of fibroblast growth factor receptor (FGFR) signaling. By engineering a chimeric receptor, the authors demonstrate that FGFR intracellular signaling can be controlled in space and time by blue light.

    View details for DOI 10.1016/j.chembiol.2014.07.004

    View details for PubMedID 25036775

  • Light-Mediated Kinetic Control Reveals the Temporal Effect of the Raf/MEK/ERK Pathway in PC12 Cell Neurite Outgrowth PLOS ONE Zhang, K., Duan, L., Ong, Q., Lin, Z., Varman, P. M., Sung, K., Cui, B. 2014; 9 (3)
  • Divergence of the long-wavelength collective diffusion coefficient in quasi-one- and quasi-two-dimensional colloidal suspensions PHYSICAL REVIEW E Lin, B., Cui, B., Xu, X., Zangi, R., Diamant, H., Rice, S. A. 2014; 89 (2)
  • Iridium oxide nanotube electrodes for sensitive and prolonged intracellular measurement of action potentials NATURE COMMUNICATIONS Lin, Z. C., Xie, C., Osakada, Y., Cui, Y., Cui, B. 2014; 5

    View details for DOI 10.1038/ncomms4206

    View details for Web of Science ID 000332663200002

  • NANOWIRE TRANSISTORS Room for manoeuvre NATURE NANOTECHNOLOGY Lin, Z. C., Cui, B. 2014; 9 (2): 94-96

    View details for DOI 10.1038/nnano.2014.10

    View details for Web of Science ID 000331069200006

    View details for PubMedID 24496276

  • Iridium oxide nanotube electrodes for sensitive and prolonged intracellular measurement of action potentials. Nature communications Lin, Z. C., Xie, C., Osakada, Y., Cui, Y., Cui, B. 2014; 5: 3206-?


    Intracellular recording of action potentials is important to understand electrically-excitable cells. Recently, vertical nanoelectrodes have been developed to achieve highly sensitive, minimally invasive and large-scale intracellular recording. It has been demonstrated that the vertical geometry is crucial for the enhanced signal detection. Here we develop nanoelectrodes of a new geometry, namely nanotubes of iridium oxide. When cardiomyocytes are cultured upon those nanotubes, the cell membrane not only wraps around the vertical tubes but also protrudes deep into the hollow centre. We show that this nanotube geometry enhances cell-electrode coupling and results in larger signals than solid nanoelectrodes. The nanotube electrodes also afford much longer intracellular access and are minimally invasive, making it possible to achieve stable recording up to an hour in a single session and more than 8 days of consecutive daily recording. This study suggests that the nanoelectrode performance can be significantly improved by optimizing the electrode geometry.

    View details for DOI 10.1038/ncomms4206

    View details for PubMedID 24487777

  • Hard X-ray-induced optical luminescence via biomolecule-directed metal clusters CHEMICAL COMMUNICATIONS Osakada, Y., Pratx, G., Sun, C., Sakamoto, M., Ahmad, M., Volotskova, O., Ong, Q., Teranishi, T., Harada, Y., Xing, L., Cui, B. 2014; 50 (27): 3549-3551


    Here, we demonstrate that biomolecule-directed metal clusters are applicable in the study of hard X-ray excited optical luminescence, promising a new direction in the development of novel X-ray-activated imaging probes.

    View details for DOI 10.1039/c3cc48661c

    View details for Web of Science ID 000332483200003

    View details for PubMedID 24463467

  • Light-mediated kinetic control reveals the temporal effect of the Raf/MEK/ERK pathway in PC12 cell neurite outgrowth. PloS one Zhang, K., Duan, L., Ong, Q., Lin, Z., Varman, P. M., Sung, K., Cui, B. 2014; 9 (3)


    It has been proposed that differential activation kinetics allows cells to use a common set of signaling pathways to specify distinct cellular outcomes. For example, nerve growth factor (NGF) and epidermal growth factor (EGF) induce different activation kinetics of the Raf/MEK/ERK signaling pathway and result in differentiation and proliferation, respectively. However, a direct and quantitative linkage between the temporal profile of Raf/MEK/ERK activation and the cellular outputs has not been established due to a lack of means to precisely perturb its signaling kinetics. Here, we construct a light-gated protein-protein interaction system to regulate the activation pattern of the Raf/MEK/ERK signaling pathway. Light-induced activation of the Raf/MEK/ERK cascade leads to significant neurite outgrowth in rat PC12 pheochromocytoma cell lines in the absence of growth factors. Compared with NGF stimulation, light stimulation induces longer but fewer neurites. Intermittent on/off illumination reveals that cells achieve maximum neurite outgrowth if the off-time duration per cycle is shorter than 45 min. Overall, light-mediated kinetic control enables precise dissection of the temporal dimension within the intracellular signal transduction network.

    View details for DOI 10.1371/journal.pone.0092917

    View details for PubMedID 24667437

  • Defective Axonal Transport of Rab7 GTPase Results in Dysregulated Trophic Signaling. journal of neuroscience Zhang, K., Fishel Ben Kenan, R., Osakada, Y., Xu, W., Sinit, R. S., Chen, L., Zhao, X., Chen, J., Cui, B., Wu, C. 2013; 33 (17): 7451-7462


    Retrograde trophic signaling of nerve growth factor (NGF) supports neuronal survival and differentiation. Dysregulated trophic signaling could lead to various neurological disorders. Charcot-Marie-Tooth type 2B (CMT2B) is one of the most common inherited peripheral neuropathies characterized by severe terminal axonal loss. Genetic analysis of human CMT2B patients has revealed four missense point mutations in Rab7, a small GTPase that regulates late endosomal/lysosomal pathways, but the exact pathological mechanism remains poorly understood. Here, we show that these Rab7 mutants dysregulated axonal transport and diminished the retrograde signaling of NGF and its TrkA receptor. We found that all CMT2B Rab7 mutants were transported significantly faster than Rab7(wt) in the anterograde direction, accompanied with an increased percentile of anterograde Rab7-vesicles within axons of rat E15.5 dorsal root ganglion (DRG) neurons. In PC12M cells, the CMT2B Rab7 mutants drastically reduced the level of surface TrkA and NGF binding, presumably by premature degradation of TrkA. On the other hand, siRNA knock-down of endogenous Rab7 led to the appearance of large TrkA puncta in enlarged Rab5-early endosomes within the cytoplasm, suggesting delayed TrkA degradation. We also show that CMT2B Rab7 mutants markedly impaired NGF-induced Erk1/2 activation and differentiation in PC12M cells. Further analysis revealed that CMT2B Rab7 mutants caused axonal degeneration in rat E15.5 DRG neurons. We propose that Rab7 mutants induce premature degradation of retrograde NGF-TrkA trophic signaling, which may potentially contribute to the CMT2B disease.

    View details for DOI 10.1523/JNEUROSCI.4322-12.2013

    View details for PubMedID 23616551

  • Defective Axonal Transport of Rab7 GTPase Results in Dysregulated Trophic Signaling JOURNAL OF NEUROSCIENCE Zhang, K., Ben Kenan, R. F., Osakada, Y., Xu, W., Sinit, R. S., Chen, L., Zhao, X., Chen, J., Cui, B., Wu, C. 2013; 33 (17): 7451-7462
  • X-ray excitable luminescent polymer dots doped with an iridium(III) complex CHEMICAL COMMUNICATIONS Osakada, Y., Pratx, G., Hanson, L., Solomon, P. E., Xing, L., Cui, B. 2013; 49 (39): 4319-4321


    In this study, cyclometalated iridium(III) complex-doped polymer dots were synthesized and shown to emit luminescence upon X-ray irradiation, potentially serving as a new probe for molecular imaging during X-ray computed tomography.

    View details for DOI 10.1039/c2cc37169c

    View details for Web of Science ID 000317931500063

    View details for PubMedID 23320256

  • Characterization of the Cell-Nanopillar Interface by Transmission Electron Microscopy NANO LETTERS Hanson, L., Lin, Z. C., Xie, C., Cui, Y., Cui, B. 2012; 12 (11): 5815-5820


    Vertically aligned nanopillars can serve as excellent electrical, optical and mechanical platforms for biological studies. However, revealing the nature of the interface between the cell and the nanopillar is very challenging. In particular, a matter of debate is whether the cell membrane remains intact around the nanopillar. Here we present a detailed characterization of the cell-nanopillar interface by transmission electron microscopy. We examined cortical neurons growing on nanopillars with diameter 50-500 nm and heights 0.5-2 ?m. We found that on nanopillars less than 300 nm in diameter, the cell membrane wraps around the entirety of the nanopillar without the nanopillar penetrating into the interior of the cell. On the other hand, the cell sits on top of arrays of larger, closely spaced nanopillars. We also observed that the membrane-surface gap of both cell bodies and neurites is smaller for nanopillars than for a flat substrate. These results support a tight interaction between the cell membrane and the nanopillars and previous findings of excellent sealing in electrophysiology recordings using nanopillar electrodes.

    View details for DOI 10.1021/nl303163y

    View details for Web of Science ID 000311244400064

    View details for PubMedID 23030066

  • Intracellular recording of action potentials by nanopillar electroporation NATURE NANOTECHNOLOGY Xie, C., Lin, Z., Hanson, L., Cui, Y., Cui, B. 2012; 7 (3): 185-190


    Action potentials have a central role in the nervous system and in many cellular processes, notably those involving ion channels. The accurate measurement of action potentials requires efficient coupling between the cell membrane and the measuring electrodes. Intracellular recording methods such as patch clamping involve measuring the voltage or current across the cell membrane by accessing the cell interior with an electrode, allowing both the amplitude and shape of the action potentials to be recorded faithfully with high signal-to-noise ratios. However, the invasive nature of intracellular methods usually limits the recording time to a few hours, and their complexity makes it difficult to simultaneously record more than a few cells. Extracellular recording methods, such as multielectrode arrays and multitransistor arrays, are non-invasive and allow long-term and multiplexed measurements. However, extracellular recording sacrifices the one-to-one correspondence between the cells and electrodes, and also suffers from significantly reduced signal strength and quality. Extracellular techniques are not, therefore, able to record action potentials with the accuracy needed to explore the properties of ion channels. As a result, the pharmacological screening of ion-channel drugs is usually performed by low-throughput intracellular recording methods. The use of nanowire transistors, nanotube-coupled transistors and micro gold-spine and related electrodes can significantly improve the signal strength of recorded action potentials. Here, we show that vertical nanopillar electrodes can record both the extracellular and intracellular action potentials of cultured cardiomyocytes over a long period of time with excellent signal strength and quality. Moreover, it is possible to repeatedly switch between extracellular and intracellular recording by nanoscale electroporation and resealing processes. Furthermore, vertical nanopillar electrodes can detect subtle changes in action potentials induced by drugs that target ion channels.

    View details for DOI 10.1038/NNANO.2012.8

    View details for Web of Science ID 000301186300012

    View details for PubMedID 22327876

  • Neurotrophin Signaling via Long-Distance Axonal Transport ANNUAL REVIEW OF PHYSICAL CHEMISTRY, VOL 63 Chowdary, P. D., Che, D. L., Cui, B. 2012; 63: 571-594


    Neurotrophins are a family of target-derived growth factors that support survival, development, and maintenance of innervating neurons. Owing to the unique architecture of neurons, neurotrophins that act locally on the axonal terminals must convey their signals across the entire axon for subsequent regulation of gene transcription in the cell nucleus. This long-distance retrograde signaling, a motor-driven process that can take hours or days, has been a subject of intense interest. In the last decade, live-cell imaging with high sensitivity has significantly increased our capability to track the transport of neurotrophins, their receptors, and subsequent signals in real time. This review summarizes recent research progress in understanding neurotrophin-receptor interactions at the axonal terminal and their transport dynamics along the axon. We emphasize high-resolution studies at the single-molecule level and also discuss recent technical advances in the field.

    View details for DOI 10.1146/annurev-physchem-032511-143704

    View details for Web of Science ID 000304203500026

    View details for PubMedID 22404590

  • Functional characterization and axonal transport of quantum dot labeled BDNF INTEGRATIVE BIOLOGY Xie, W., Zhang, K., Cui, B. 2012; 4 (8): 953-960


    Brain derived neurotrophic factor (BDNF) plays a key role in the growth, development and maintenance of the central and peripheral nervous systems. Exogenous BDNF activates its membrane receptors at the axon terminal, and subsequently sends regulation signals to the cell body. To understand how a BDNF signal propagates in neurons, it is important to follow the trafficking of BDNF after it is internalized at the axon terminal. Here we labeled BDNF with bright, photostable quantum dots (QD-BDNF) and followed the axonal transport of QD-BDNF in real time in hippocampal neurons. We showed that QD-BDNF was able to bind BDNF receptors and activate downstream signaling pathways. When QD-BDNF was applied to the distal axons of hippocampal neurons, it was observed to be actively transported toward the cell body at an average speed of 1.11 ± 0.05 ?m s(-1). A closer examination revealed that QD-BDNF was transported by both discrete endosomes and multivesicular body-like structures. Our results showed that QD-BDNF could be used to track the movement of exogenous BDNF in neurons over long distances and to study the signaling organelles that contain BDNF.

    View details for DOI 10.1039/c2ib20062g

    View details for Web of Science ID 000306708500014

    View details for PubMedID 22772872

  • Diarylethene doped biocompatible polymer dots for fluorescence switching CHEMICAL COMMUNICATIONS Osakada, Y., Hanson, L., Cui, B. 2012; 48 (27): 3285-3287


    The photochromic molecule diarylethene works as a "toggle switch" for biocompatible fluorescence polymer dots and enables fluorescence switching in biological samples.

    View details for DOI 10.1039/c2cc18085e

    View details for Web of Science ID 000301057400004

    View details for PubMedID 22294244

  • Automated Image Analysis for Tracking Cargo Transport in Axons MICROSCOPY RESEARCH AND TECHNIQUE Zhang, K., Osakada, Y., Xie, W., Cui, B. 2011; 74 (7): 605-613


    The dynamics of cargo movement in axons encodes crucial information about the underlying regulatory mechanisms of the axonal transport process in neurons, a central problem in understanding many neurodegenerative diseases. Quantitative analysis of cargo dynamics in axons usually includes three steps: (1) acquiring time-lapse image series, (2) localizing individual cargos at each time step, and (3) constructing dynamic trajectories for kinetic analysis. Currently, the later two steps are usually carried out with substantial human intervention. This article presents a method of automatic image analysis aiming for constructing cargo trajectories with higher data processing throughput, better spatial resolution, and minimal human intervention. The method is based on novel applications of several algorithms including 2D kymograph construction, seed points detection, trajectory curve tracing, back-projection to extract spatial information, and position refining using a 2D Gaussian fitting. This method is sufficiently robust for usage on images with low signal-to-noise ratio, such as those from single molecule experiments. The method was experimentally validated by tracking the axonal transport of quantum dot and DiI fluorophore-labeled vesicles in dorsal root ganglia neurons.

    View details for DOI 10.1002/jemt.20934

    View details for Web of Science ID 000292570900005

    View details for PubMedID 20945466

  • A Microfluidic Positioning Chamber for Long-Term Live-Cell Imaging MICROSCOPY RESEARCH AND TECHNIQUE Hanson, L., Cui, L., Xie, C., Cui, B. 2011; 74 (6): 496-501


    We report a microfluidic positioning chamber (MPC) that can rapidly and repeatedly relocate the same imaging area on a microscope stage. The "roof" of the microfluidic chamber was printed with serials of coordinate numbers that act as positioning marks for mammalian cells that grow attached to the "floor" of the microfluidic chamber. MPC cell culture chamber provided a simple solution for tracking the same cell or groups of cells over days or weeks. The positioning marks were used to register time-lapse images of the same imaging area to single-pixel accuracy. Using MPC cell culture chamber, we tracked the migration, division, and differentiation of individual PC12 cells for over a week using bright field and fluorescence imaging.

    View details for DOI 10.1002/jemt.20937

    View details for Web of Science ID 000291539200004

    View details for PubMedID 20936672

  • Vertical nanopillars for highly localized fluorescence imaging PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Xie, C., Hanson, L., Cui, Y., Cui, B. 2011; 108 (10): 3894-3899


    Observing individual molecules in a complex environment by fluorescence microscopy is becoming increasingly important in biological and medical research, for which critical reduction of observation volume is required. Here, we demonstrate the use of vertically aligned silicon dioxide nanopillars to achieve below-the-diffraction-limit observation volume in vitro and inside live cells. With a diameter much smaller than the wavelength of visible light, a transparent silicon dioxide nanopillar embedded in a nontransparent substrate restricts the propagation of light and affords evanescence wave excitation along its vertical surface. This effect creates highly confined illumination volume that selectively excites fluorescence molecules in the vicinity of the nanopillar. We show that this nanopillar illumination can be used for in vitro single-molecule detection at high fluorophore concentrations. In addition, we demonstrate that vertical nanopillars interface tightly with live cells and function as highly localized light sources inside the cell. Furthermore, specific chemical modification of the nanopillar surface makes it possible to locally recruit proteins of interest and simultaneously observe their behavior within the complex, crowded environment of the cell.

    View details for DOI 10.1073/pnas.1015589108

    View details for Web of Science ID 000288120400019

    View details for PubMedID 21368157

  • Real-time visualization of axonal transport in neurons. Methods in molecular biology (Clifton, N.J.) Osakada, Y., Cui, B. 2011; 670: 231-243


    The normal function of neurons depends on the integrity of microtubule-dependent transport of cellular materials and organelles to/from their cell bodies or axon terminus. In this chapter, we describe the design and implementation of a fluorescence imaging method to visualize axonal transport in neurons directly. We combine a pseudo total internal reflection microscopy, quantum dot fluorescence labeling, microfluidic neuronal culture chamber, and single molecule detection methods to achieve a high spatial and temporal resolution in tracking nerve growth factor transport in dorsal root ganglia neurons.

    View details for DOI 10.1007/978-1-60761-744-0_16

    View details for PubMedID 20967594

  • Tau Reduction Prevents A beta-Induced Defects in Axonal Transport SCIENCE Vossel, K. A., Zhang, K., Brodbeck, J., Daub, A. C., Sharma, P., Finkbeiner, S., Cui, B., Mucke, L. 2010; 330 (6001): 198-U52


    Amyloid-? (A?) peptides, derived from the amyloid precursor protein, and the microtubule-associated protein tau are key pathogenic factors in Alzheimer's disease (AD). How exactly they impair cognitive functions is unknown. We assessed the effects of A? and tau on axonal transport of mitochondria and the neurotrophin receptor TrkA, cargoes that are critical for neuronal function and survival and whose distributions are altered in AD. A? oligomers rapidly inhibited axonal transport of these cargoes in wild-type neurons. Lowering tau levels prevented these defects without affecting baseline axonal transport. Thus, A? requires tau to impair axonal transport, and tau reduction protects against A?-induced axonal transport defects.

    View details for DOI 10.1126/science.1194653

    View details for Web of Science ID 000282644600034

    View details for PubMedID 20829454

  • Noninvasive Neuron Pinning with Nanopillar Arrays NANO LETTERS Xie, C., Hanson, L., Xie, W., Lin, Z., Cui, B., Cui, Y. 2010; 10 (10): 4020-4024


    Cell migration in a cultured neuronal network presents an obstacle to selectively measuring the activity of the same neuron over a long period of time. Here we report the use of nanopillar arrays to pin the position of neurons in a noninvasive manner. Vertical nanopillars protruding from the surface serve as geometrically better focal adhesion points for cell attachment than a flat surface. The cell body mobility is significantly reduced from 57.8 ?m on a flat surface to 3.9 ?m on nanopillars over a 5 day period. Yet, neurons growing on nanopillar arrays show a growth pattern that does not differ in any significant way from that seen on a flat substrate. Notably, while the cell bodies of neurons are efficiently anchored by the nanopillars, the axons and dendrites are free to grow and elongate into the surrounding area to develop a neuronal network, which opens up opportunities for long-term study of the same neurons in connected networks.

    View details for DOI 10.1021/nl101950x

    View details for Web of Science ID 000282727600038

    View details for PubMedID 20815404

  • Hydrodynamic interactions in ribbon channels: From quasi-one-dimensional to quasi-two-dimensional behavior PHYSICAL REVIEW E Novikov, S., Rice, S. A., Cui, B., Diamant, H., Lin, B. 2010; 82 (3)


    We present a study of the dynamics of confined suspensions whose dimensionality is intermediate between quasi-one-dimensional and quasi-two-dimensional (q2D) using microfluidic channels of various widths. The crossover between the two limiting behaviors is found to occur to different extent for different dynamic correlations between a pair of particles. In particular, the transverse coupling diffusion coefficient of particle pairs significantly deviates from its q2D form even in surprisingly wide channels.

    View details for DOI 10.1103/PhysRevE.82.031403

    View details for Web of Science ID 000281741000002

    View details for PubMedID 21230073

  • Single-molecule imaging of NGF axonal transport in microfluidic devices LAB ON A CHIP Zhang, K., Osakada, Y., Vrljic, M., Chen, L., Mudrakola, H. V., Cui, B. 2010; 10 (19): 2566-2573


    Nerve growth factor (NGF) signaling begins at the nerve terminal, where it binds and activates membrane receptors and subsequently carries the cell-survival signal to the cell body through the axon. A recent study revealed that the majority of endosomes contain a single NGF molecule, which makes single-molecule imaging an essential tool for NGF studies. Despite being an increasingly popular technique, single-molecule imaging in live cells is often limited by background fluorescence. Here, we employed a microfluidic culture platform to achieve background reduction for single-molecule imaging in live neurons. Microfluidic devices guide the growth of neurons and allow separately controlled microenvironment for cell bodies or axon termini. Designs of microfluidic devices were optimized and a three-compartment device successfully achieved direct observation of axonal transport of single NGF when quantum dot labeled NGF (Qdot-NGF) was applied only to the distal-axon compartment while imaging was carried out exclusively in the cell-body compartment. Qdot-NGF was shown to move exclusively toward the cell body with a characteristic stop-and-go pattern of movements. Measurements at various temperatures show that the rate of NGF retrograde transport decreased exponentially over the range of 36-14 degrees C. A 10 degrees C decrease in temperature resulted in a threefold decrease in the rate of NGF retrograde transport. Our successful measurements of NGF transport suggest that the microfluidic device can serve as a unique platform for single-molecule imaging of molecular processes in neurons.

    View details for DOI 10.1039/c003385e

    View details for Web of Science ID 000281614900012

    View details for PubMedID 20623041

  • Optically Resolving Individual Microtubules in Live Axons STRUCTURE Mudrakola, H. V., Zhang, K., Cui, B. 2009; 17 (11): 1433-1441


    Microtubules are essential cytoskeletal tracks for cargo transportation in axons and also serve as the primary structural scaffold of neurons. Structural assembly, stability, and dynamics of axonal microtubules are of great interest for understanding neuronal functions and pathologies. However, microtubules are so densely packed in axons that their separations are well below the diffraction limit of light, which precludes using optical microscopy for live-cell studies. Here, we present a single-molecule imaging method capable of resolving individual microtubules in live axons. In our method, unlabeled microtubules are revealed by following individual axonal cargos that travel along them. We resolved more than six microtubules in a 1 microm diameter axon by real-time tracking of endosomes containing quantum dots. Our live-cell study also provided direct evidence that endosomes switch between microtubules while traveling along axons, which has been proposed to be the primary means for axonal cargos to effectively navigate through the crowded axoplasmic environment.

    View details for DOI 10.1016/j.str.2009.09.008

    View details for Web of Science ID 000272011500005

    View details for PubMedID 19913478

  • The Quasi-One-Dimensional Colloid Fluid Revisited JOURNAL OF PHYSICAL CHEMISTRY B Lin, B., Valley, D., Meron, M., Cui, B., Ho, H. M., Rice, S. A. 2009; 113 (42): 13742-13751


    We report the results of studies of the pair correlation function and equation of state of a quasi-one-dimensional colloid suspension, focusing attention on the behavior in the density range near close packing. Our data show that, despite deviations from true one-dimensional geometry, the colloid fluid is well described as a hard rod Tonks fluid. In our experimental realization, the colloid suspension does not wet the confining walls, one consequence of which is a surface tension induced weak attractive interaction between the particles. The reality of this interaction is confirmed after correction of the raw experimental data for overlap of the optical images of particles that are nearly in contact and by an alternative particle location algorithm based on edge location.

    View details for DOI 10.1021/jp9018734

    View details for Web of Science ID 000270670800010

    View details for PubMedID 19569626

  • Structure of quasi-one-dimensional ribbon colloid suspensions PHYSICAL REVIEW E Stratton, T. R., Novikov, S., Qato, R., Villarreal, S., Cui, B., Rice, S. A., Lin, B. 2009; 79 (3)


    We report the results of an experimental study of a colloid fluid confined to a quasi-one-dimensional (q1D) ribbon channel as a function of channel width and colloid density. Our findings confirm the principal predictions of previous theoretical studies of such systems. These are (1) that the density distribution of the liquid transverse to the ribbon channel exhibits stratification; (2) that even at the highest density the order along the strata, as measured by the longitudinal pair correlation function, is characteristic of a liquid; and (3) the q1D pair correlation functions in different strata exhibit anisotropic behavior resembling that found in a Monte Carlo simulation for the in-plane pair correlation function of a hard sphere fluid in a planar slit.

    View details for DOI 10.1103/PhysRevE.79.031406

    View details for Web of Science ID 000264767300067

    View details for PubMedID 19391943

  • The coming of age of axonal neurotrophin signaling endosomes JOURNAL OF PROTEOMICS Wu, C., Cui, B., He, L., Chen, L., Mobley, W. C. 2009; 72 (1): 46-55


    Neurons of both the central and the peripheral nervous system are critically dependent on neurotrophic signals for their survival and differentiation. The trophic signal is originated at the axonal terminals that innervate the target(s). It has been well established that the signal must be retrogradely transported back to the cell body to exert its trophic effect. Among the many forms of transmitted signals, the signaling endosome serves as a primary means to ensure that the retrograde signal is delivered to the cell body with sufficient fidelity and specificity. Recent evidence suggests that disruption of axonal transport of neurotrophin signals may contribute to neurodegenerative diseases such as Alzheimer's disease and Down syndrome. However, the identity of the endocytic vesicular carrier(s), and the mechanisms involved in retrogradely transporting the signaling complexes remain a matter of debate. In this review, we summarize current insights that are mainly based on classical hypothesis-driven research, and we emphasize the urgent needs to carry out proteomics to resolve the controversies in the field.

    View details for DOI 10.1016/j.jprot.2008.10.007

    View details for Web of Science ID 000264320700006

    View details for PubMedID 19028611

  • Anomalous behavior of the depletion potential in quasi-two-dimensional binary mixtures PHYSICAL REVIEW E Cui, B., Lin, B., Frydel, D., Rice, S. A. 2005; 72 (2)


    We report an experimental determination of the depletion interaction between a pair of large colloid particles present in a binary colloid mixture that has a high density of large particles and is tightly confined between two parallel plates, as a function of the small colloid particle density. The bare interaction between the large particles in the one component large colloid suspension, and the effective potential between the large particles in the binary colloid suspension represented as a pseudo-one-component fluid, were obtained by inverting the Ornstein-Zernike equation with the hypernetted chain closure. The depletion interaction is defined by subtracting the bare potential from the effective potential at fixed large colloid density. We find that the depletion potential in the quasi-two-dimensional (Q2D) system is purely attractive and short ranged as described by Asakura-Oosawa model. However, the depth of the depletion potential is found to be almost an order of magnitude larger than the counterpart depletion potential predicted for the same density and diameter ratio in a three-dimensional system. Although it is expected that the confining walls in the Q2D geometry enhance the excluded volume effects that generate entropic attraction, the observed enhancement is much larger than predicted for a Q2D binary mixture of hard spheres. We speculate that this anomalously strong confinement-induced depletion potential is a signature of characteristics of the real confined binary colloid mixture that are not included in any extant theory of the depletion interaction, specifically the omission of the role of the solvent in those theories. One such characteristic could be differential wall or particle wetting that generates a wall induced one-particle effective potential that confines the centers of the small particles to lie closer to the midplane between the walls than expected from the wall separation and the direct particle-wall interaction, thereby enhancing the depletion interaction.

    View details for DOI 10.1103/PhysRevE.72.021402

    View details for Web of Science ID 000231564000027

    View details for PubMedID 16196560