We are a discovery-driven research group working at the interface between statistical physics, developmental biology, and bioengineering. We combine quantitative organism-wide fluorescence imaging ("deep imaging"), functional genomics ("deep sequencing"), and statistical modeling to study systems biology and evolutionary cell biology of flatworms, including free living planarians and parasitic flukes. Using these animals, we seek to understand quantitatively the fundamental rules that control stem cell collective behavior to optimize tissue regeneration, remolding, and adaptation.
Honors & Awards
Baxter Faculty Scholar Award, Donald E. and Delia B. Baxter Foundation (2016)
Career Award at the Scientific Interface, Burroughs Wellcome Fund (2013)
Ross J. Martin Award, University of Illinois (2012)
Victor K. LaMer Award, American Chemical Society (2012)
Institute for Genomic Biology Fellowship, University of Illinois (2011)
Frank J. Padden, Jr. Award, American Physical Society (2010)
Mavis Memorial Fund Scholarship Award, University of Illinois (2010)
Boards, Advisory Committees, Professional Organizations
Faculty Fellow, Stanford Center for Innovation in Global Health (2015 - Present)
Ph.D., University of Illinois, Urbana-Champaign, Materials Science (2011)
M.S., B.S., Zhejiang University, Materials Science (2006)
- Special Topics in Development and Cancer: Evolutionary and Quantitative Perspectives
BIOE 219, DBIO 219 (Spr)
Independent Studies (4)
- Bioengineering Problems and Experimental Investigation
BIOE 191 (Win)
- Directed Investigation
BIOE 392 (Aut, Win, Spr)
- Directed Reading in Biophysics
BIOPHYS 399 (Win, Spr)
- Graduate Research
BIOPHYS 300 (Win, Spr)
- Bioengineering Problems and Experimental Investigation
Postdoctoral Faculty Sponsor
Memoryless self-reinforcing directionality in endosomal active transport within living cells
2015; 14 (6): 589-593
In contrast to Brownian transport, the active motility of microbes, cells, animals and even humans often follows another random process known as truncated Lévy walk. These stochastic motions are characterized by clustered small steps and intermittent longer jumps that often extend towards the size of the entire system. As there are repeated suggestions, although disagreement, that Lévy walks have functional advantages over Brownian motion in random searching and transport kinetics, their intentional engineering into active materials could be useful. Here, we show experimentally in the classic active matter system of intracellular trafficking that Brownian-like steps self-organize into truncated Lévy walks through an apparent time-independent positive feedback such that directional persistence increases with the distance travelled persistently. A molecular model that allows the maximum output of the active propelling forces to fluctuate slowly fits the experiments quantitatively. Our findings offer design principles for programming efficient transport in active materials.
View details for DOI 10.1038/NMAT4239
View details for Web of Science ID 000354801500021
View details for PubMedID 25822692
Bursts of Active Transport in Living Cells
PHYSICAL REVIEW LETTERS
2013; 111 (20)
We show, using a large new data set, that the temporally resolved speed of active cargo transport in living cells follows a scaling law over several decades of time and length. The statistical regularities display a time-averaged shape that we interpret to reflect stress buildup, followed by rapid release. The scaling power law agrees quantitatively with those reported in inanimate systems (jammed colloids and granular media, and magnetic Barkhausen noise), suggesting a common origin in pushing through a crowded environment in a weak force regime. The implied regulation of the speed of active cellular transport due to environmental obstruction results in bursts of speed and acceleration. These findings extend the classical notion of molecular crowding.
View details for DOI 10.1103/PhysRevLett.111.208102
View details for Web of Science ID 000327243600026
View details for PubMedID 24289710
Functional genomic characterization of neoblast-like stem cells in larval Schistosoma mansoni
Schistosomes infect hundreds of millions of people in the developing world. Transmission of these parasites relies on a stem cell-driven, clonal expansion of larvae inside a molluscan intermediate host. How this novel asexual reproductive strategy relates to current models of stem cell maintenance and germline specification is unclear. Here, we demonstrate that this proliferative larval cell population (germinal cells) shares some molecular signatures with stem cells from diverse organisms, in particular neoblasts of planarians (free-living relatives of schistosomes). We identify two distinct germinal cell lineages that differ in their proliferation kinetics and expression of a nanos ortholog. We show that a vasa/PL10 homolog is required for proliferation and maintenance of both populations, whereas argonaute2 and a fibroblast growth factor receptor-encoding gene are required only for nanos-negative cells. Our results suggest that an ancient stem cell-based developmental program may have enabled the evolution of the complex life cycle of parasitic flatworms. DOI:http://dx.doi.org/10.7554/eLife.00768.001.
View details for DOI 10.7554/eLife.00768
View details for Web of Science ID 000328622300001
View details for PubMedID 23908765
Adult somatic stem cells in the human parasite Schistosoma mansoni
2013; 494 (7438): 476-479
Schistosomiasis is among the most prevalent human parasitic diseases, affecting more than 200 million people worldwide. The aetiological agents of this disease are trematode flatworms (Schistosoma) that live and lay eggs within the vasculature of the host. These eggs lodge in host tissues, causing inflammatory responses that are the primary cause of morbidity. Because these parasites can live and reproduce within human hosts for decades, elucidating the mechanisms that promote their longevity is of fundamental importance. Although adult pluripotent stem cells, called neoblasts, drive long-term homeostatic tissue maintenance in long-lived free-living flatworms (for example, planarians), and neoblast-like cells have been described in some parasitic tapeworms, little is known about whether similar cell types exist in any trematode species. Here we describe a population of neoblast-like cells in the trematode Schistosoma mansoni. These cells resemble planarian neoblasts morphologically and share their ability to proliferate and differentiate into derivatives of multiple germ layers. Capitalizing on available genomic resources and RNA-seq-based gene expression profiling, we find that these schistosome neoblast-like cells express a fibroblast growth factor receptor orthologue. Using RNA interference we demonstrate that this gene is required for the maintenance of these neoblast-like cells. Our observations indicate that adaptation of developmental strategies shared by free-living ancestors to modern-day schistosomes probably contributed to the success of these animals as long-lived obligate parasites. We expect that future studies deciphering the function of these neoblast-like cells will have important implications for understanding the biology of these devastating parasites.
View details for DOI 10.1038/nature11924
View details for Web of Science ID 000315661500038
View details for PubMedID 23426263
- When Brownian diffusion is not Gaussian NATURE MATERIALS 2012; 11 (6): 481-485
Confining Potential when a Biopolymer Filament Reptates
PHYSICAL REVIEW LETTERS
2010; 104 (11)
Using single-molecule fluorescence imaging, we track Brownian motion perpendicular to the contour of tightly entangled F-actin filaments and extract the confining potential. The chain localization presents a small-displacement Hookean regime followed by a large amplitude regime where the effective restoring force is independent of displacement. The implied heterogeneity characterized by a distribution of tube width is modeled.
View details for DOI 10.1103/PhysRevLett.104.118301
View details for Web of Science ID 000275802600045
View details for PubMedID 20366503
Anomalous yet Brownian
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
2009; 106 (36): 15160-15164
We describe experiments using single-particle tracking in which mean-square displacement is simply proportional to time (Fickian), yet the distribution of displacement probability is not Gaussian as should be expected of a classical random walk but, instead, is decidedly exponential for large displacements, the decay length of the exponential being proportional to the square root of time. The first example is when colloidal beads diffuse along linear phospholipid bilayer tubes whose radius is the same as that of the beads. The second is when beads diffuse through entangled F-actin networks, bead radius being less than one-fifth of the actin network mesh size. We explore the relevance to dynamic heterogeneity in trajectory space, which has been extensively discussed regarding glassy systems. Data for the second system might suggest activated diffusion between pores in the entangled F-actin networks, in the same spirit as activated diffusion and exponential tails observed in glassy systems. But the first system shows exceptionally rapid diffusion, nearly as rapid as for identical colloids in free suspension, yet still displaying an exponential probability distribution as in the second system. Thus, although the exponential tail is reminiscent of glassy systems, in fact, these dynamics are exceptionally rapid. We also compare with particle trajectories that are at first subdiffusive but Fickian at the longest measurement times, finding that displacement probability distributions fall onto the same master curve in both regimes. The need is emphasized for experiments, theory, and computer simulation to allow definitive interpretation of this simple and clean exponential probability distribution.
View details for DOI 10.1073/pnas.0903554106
View details for Web of Science ID 000269632400015
View details for PubMedID 19666495
Nanoparticle-induced surface reconstruction of phospholipid membranes
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
2008; 105 (47): 18171-18175
The nonspecific adsorption of charged nanoparticles onto single-component phospholipid bilayers bearing phosphocholine headgroups is shown, from fluorescence and calorimetry experiments, to cause surface reconstruction at the points where nanoparticles adsorb. Nanoparticles of negative charge induce local gelation in otherwise fluid bilayers; nanoparticles of positive charge induce otherwise gelled membranes to fluidize locally. Through this mechanism, the phase state deviates from the nominal phase transition temperature by tens of degrees. This work generalizes the notions of environmentally induced surface reconstruction, prominent in metals and semiconductors. Bearing in mind that chemical composition in these single-component lipid bilayers is the same everywhere, this offers a mechanism to generate patchy functional properties in phospholipid membranes.
View details for DOI 10.1073/pnas.0807296105
View details for Web of Science ID 000261489300026
View details for PubMedID 19011086
Even Hard-Sphere Colloidal Suspensions Display Fickian Yet Non-Gaussian Diffusion
2014; 8 (4): 3331-3336
We scrutinize three decades of probability density displacement distribution in a simple colloidal suspension with hard-sphere interactions. In this index-matched and density-matched solvent, fluorescent tracer nanoparticles diffuse among matrix particles that are eight times larger, at concentrations from dilute to concentrated, over times up to when the tracer diffuses a few times its size. Displacement distributions of tracers, Gaussian in pure solvent, broaden systematically with increasing obstacle density. The onset of non-Gaussian dynamics is seen in even modestly dilute suspensions, which traditionally would be assumed to follow classic Gaussian expectation. The findings underscore, in agreement with recent studies of more esoteric soft matter systems, the prevalence of non-Gaussian yet Fickian diffusion.
View details for DOI 10.1021/nn405476t
View details for Web of Science ID 000334990600023
View details for PubMedID 24646449
Diagnosing Heterogeneous Dynamics in Single-Molecule/Particle Trajectories with Multiscale Wavelets
2013; 7 (10): 8634-8644
We describe a simple automated method to extract and quantify transient heterogeneous dynamical changes from large data sets generated in single-molecule/particle tracking experiments. Based on wavelet transform, the method transforms raw data to locally match dynamics of interest. This is accomplished using statistically adaptive universal thresholding, whose advantage is to avoid a single arbitrary threshold that might conceal individual variability across populations. How to implement this multiscale method is described, focusing on local confined diffusion separated by transient transport periods or hopping events, with three specific examples: in cell biology, biotechnology, and glassy colloid dynamics. The discussion is generalized within the framework of continuous time random walk. This computationally efficient method can run routinely on hundreds of millions of data points analyzed within an hour on a desktop personal computer.
View details for DOI 10.1021/nn402787a
View details for Web of Science ID 000326209100033
View details for PubMedID 23971739
Modular Stitching To Image Single-Molecule DNA Transport
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
2013; 135 (16): 6006-6009
For study of time-dependent conformation, all previous single-molecule imaging studies of polymer transport involve fluorescence labeling uniformly along the chain, which suffers from limited resolution due to the diffraction limit. Here we demonstrate the concept of submolecular single-molecule imaging with DNA chains assembled from DNA fragments such that a chain is labeled at designated spots with covalently attached fluorescent dyes and the chain backbone with dyes of different color. High density of dyes ensures good signal-to-noise ratio to localize the designated spots in real time with nanometer precision and prevents significant photobleaching for long-time tracking purposes. To demonstrate usefulness of this approach, we image electrophoretic transport of λ-DNA through agarose gels. The unexpected pattern is observed that one end of each molecule tends to stretch out in the electric field while the other end remains quiescent for some time before it snaps forward and the stretch-recoil cycle repeats. These features are neither predicted by prevailing theories of electrophoresis mechanism nor detectable by conventional whole-chain labeling methods, which demonstrate pragmatically the usefulness of modular stitching to reveal internal chain dynamics of single molecules.
View details for DOI 10.1021/ja4020138
View details for Web of Science ID 000318204800019
View details for PubMedID 23570269
Automated Single-Molecule Imaging To Track DNA Shape
2011; 27 (10): 6149-6154
We describe a straightforward, automated line tracking method to visualize linear macromolecules as they rearrange shape by brownian diffusion and under external fields such as electrophoresis. The analysis, implemented here with 30 ms time resolution, identifies contour lines from one end of the molecule to the other without attention to structure smaller than the optical resolution. There are three sequential stages of analysis: first, "feature finding" to discriminate signal from noise; second, "line tracking" to approximate those shapes as lines; and third, "temporal consistency check" to discriminate reasonable from unreasonable fitted conformations in the time domain. Automation makes it straightforward to accumulate vast quantities of data while excluding the unreliable parts of it. We implement this analysis on fluorescence images of λ-DNA molecules in agarose gel to demonstrate its capability to produce large data sets for subsequent statistical analysis.
View details for DOI 10.1021/la200433r
View details for Web of Science ID 000290292900050
View details for PubMedID 21510676
- Single-Molecule Methods in Polymer Science JOURNAL OF POLYMER SCIENCE PART B-POLYMER PHYSICS 2010; 48 (24): 2542-2543
The influence of polycaprolactone coating on the internalization and cytotoxicity of gold nanoparticles
NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE
2007; 3 (3): 215-223
The interaction between mesoscopic colloids and cells is largely dependent on the particle size and surface properties. Under a mild reaction condition, gold particles with an average diameter of approximately 100 nm were prepared by incubating poly(dimethylsiloxane) film in HAuCl4/acetic acid solution. The particles were then transferred into a polycaprolactone (PCL) film by thermal pressing. Bare and PCL-coated particles were obtained by control over the extent of rinsing. The bare and PCL-coated gold particles were co-cultured with ECV-304 cells to examine the particle internalization and their influence on the cell morphology and cytotoxicity. Transmission electron microcopy observed the subcellular distribution of the gold particles, which were found in the cell compartments (endosomes or lysosomes), cytoplasm, nucleic envelope, and even nucleus regardless of the existence of PCL coating. However, scanning electron microscopy and beta-tubulin staining revealed a significant change in terms of the cell morphology and cytoskeleton caused by the bare gold particles. Higher cytotoxicity was also determined for the bare gold particles. By contrast, no significant difference of the cell morphology and cytoskeleton change was caused by the PCL-coated gold particles, which have also shown lower cytotoxicity.
View details for DOI 10.1016/j.nano.2007.04.001
View details for Web of Science ID 000249325500006
View details for PubMedID 17706466
- Rings of hydrogel fabricated by a micro-transfer technique MACROMOLECULAR RAPID COMMUNICATIONS 2007; 28 (5): 567-571
Stepwise interfacial self-assembly of nanoparticles via specific DNA pairing
PHYSICAL CHEMISTRY CHEMICAL PHYSICS
2007; 9 (48): 6313-6318
In the present work, we succeeded in alternatively depositing inorganic nanoparticles and functionalized DNA bases onto the water/oil interface from the water and oil bulk phases. The ligands used were functional thymines and adenines. Their thiol and phosphate groups were used to cap inorganic nanoparticles and their thymine and adenine groups to alter the surface functionality of the nanoparticles, thus enabling a layer-by-layer growth fashion of nanoparticles at the interface. The multiple particle ligation rendered the resulting nanoparticle films rather mechanically robust. As results, the freestanding asymmetric bilayer and trilayer films, composed of negatively-charged Au, positively-charged CdTe, and/or organic Ag nanoparticles were constructed; their areas were as large as over several centimetres, depending on the sizes of the containers used. Our work should bring up a novel methodology to generate asymmetric multilayer films of nanoparticles with a defined control of electron or charge across the films.
View details for Web of Science ID 000251441100004
View details for PubMedID 18060160
Chitosan-mediated synthesis of gold nanoparticles on patterned poly(dimethylsiloxane) surfaces
2006; 7 (4): 1203-1209
Synthesis of gold nanoparticles on surfaces has been accomplished by the incubation of poly(dimethylsiloxane) (PDMS) films in tetrachloroauric(III) acid and chitosan solution at room temperature and 4 degrees C. One important point in the present study is that the synthesis selectively occurred on the PDMS surface. These observations are substantially different from the reaction in solution, in which no particles can be formed at room temperature. Computation of surface plasmon bands (SPBs) based on Mie theory suggests that the particles are partially coated by chitosan molecules, and the experimental results confirm the theoretical calculations. The proposed mechanism is that chitosan molecules adsorbed or printed on the PDMS surfaces act as reducing/stabilizing agents. Furthermore, PDMS films patterned with chitosan could induce localized synthesis of gold nanoparticles in regions capped with chitosan only. In this way, colloidal patterns were fabricated on the surfaces with high spatial selectivity simultaneously with the synthesis of the particles. Surface-induced fluorescence quenching was observed in the regions capped with gold nanoparticles as well.
View details for DOI 10.1021/bm060030f
View details for Web of Science ID 000236868800027
View details for PubMedID 16602739
Compression-inhibited pore formation of polyelectrolyte multilayers containing weak polyanions: A scanning force microscopy study
2006; 7 (3): 590-596
Morphological changes of poly(acrylic acid)/poly(diallyldimethylammonium chloride) multilayers induced by low pH were investigated by scanning force microscopy. The weakened interaction between the charged polymer chains in the protonation process is believed to be the reason for this variation. Kinetic studies have shown that during protonation phase separation and dissociation of the multilayers took place successively. The compression of the multilayers, however, caused a transition of the multilayers from a rubbery state to a glassy state. As a result, the closely compacted multilayers lost their sensitivity to pH change. An increase of electrostatic and hydrophobic interactions, can decrease the free energy of the multilayers, and stabilize the films. By compression of the multilayers with a rubber stamp having geometric patterns, films with spatially localized pores were produced.
View details for DOI 10.1002/cphc.200500369
View details for Web of Science ID 000236300600010
View details for PubMedID 16425342
- Biologically driven assembly of polyelectrolyte microcapsule patterns to fabricate microreactor arrays ANGEWANDTE CHEMIE-INTERNATIONAL EDITION 2006; 45 (10): 1560-1563
Loading and release behaviors of compressed polyelectrolyte multilayers for small dye molecules
JOURNAL OF PHYSICAL CHEMISTRY B
2005; 109 (11): 4887-4892
Loading and release behaviors of compressed polyelectrolyte multilayers composed of poly(styrenesulfonate sodium salt) and poly(diallyldimethylammonium chloride) were investigated using fluorescein and rhodamine 6G as indicators by confocal laser scanning microcopy, fluorescence spectroscopy, and UV-vis spectroscopy. Compression of the multilayers resulted in a more densely packed microstructure, leading to the decrease of fluorescence intensity of the incorporated probes to 80% of its initial value, and much slower releasing rate as well as smaller releasing amount regardless of the types of the probes and the presence of salt. Utilizing the difference of loading and release rates between the compressed and the uncompressed regions, arrays of dye reservoirs have been fabricated on a chemical homogeneous but physical heterogeneous multilayer film.
View details for DOI 10.1021/jp0450282
View details for Web of Science ID 000227734500013
View details for PubMedID 16863143
- Physical-co-chemical multicomponent micropatterns on polymer surfaces by thermal pressing method CHEMISTRY OF MATERIALS 2004; 16 (24): 4859-?
- Irreversible compression of polyelectrolyte multilayers MACROMOLECULES 2004; 37 (24): 8836-8839
- Selective adsorption of microcapsules on patterned polyelectrolyte multilayers ADVANCED MATERIALS 2004; 16 (21): 1940-?