Bio


My laboratory employs diverse interdisciplinary methods of inquiry to understand the relationships among cell shape detection, determination, and maintenance in bacteria. Cell shape plays a critical role in regulating many physiological functions, yet little is known about how the wide variety of cell shapes are determined and maintained. Inside the cell, many proteins organize and segregate, but how they detect and respond to the cellular morphology to end up at the right place at the right time is also largely mysterious. The group uses a combination of analytical, computational, and experimental approaches to probe physical mechanisms of shape-related self-organization in protein networks, membranes, and the cell wall. Current topics of interest are (i) cell-wall biosynthesis, (ii) the regulation and mechanics of cell division, (iii) membrane organization, and (iv) membrane-mediated protein interactions. Ultimately, the manipulation of cell shape may provide a direct tool for engineering complex cellular behaviors.

Academic Appointments


Honors & Awards


  • Helen Hay Whitney Fellowship, Helen Hay Whitney Foundation (2005-2008)
  • NIH Director's New Innovator Award, National Institutes of Health (2009-2014)
  • CAREER Award, National Science Foundation (2012-2017)

Professional Education


  • Ph. D., MIT, Physics (2004)
  • M. Phil., Cambridge University, Physics (1999)
  • B.S., Caltech, Physics/Mathematics (1998)

Current Research and Scholarly Interests


We primarily focus on bacteria, in which the exquisite patterning of the interior in both space and time is critical for a wide variety of cellular functions. The wide variety of shapes and sizes that bacteria take on can be used as synthetic environment for studying the establishment of intracellular organization and the cellular response to perturbations in morphology. Ultimately, the manipulation of cell shape may provide a direct tool for engineering complex cellular behaviors.

Currently, we are interested in (i) the role of the cell wall in cell-shape determination, (ii) the regulation and mechanics of the cell cycle and cell division, (iii) the spatial and temporal organization of the membrane, (iv) the role of the membrane in transmembrane-protein interactions and ion channel gating, and (v) collective behavior in bacteria.

Journal Articles


  • Effects of polymerization and nucleotide identity on the conformational dynamics of the bacterial actin homolog MreB. Proceedings of the National Academy of Sciences of the United States of America Colavin, A., Hsin, J., Huang, K. C. 2014; 111 (9): 3585-3590

    Abstract

    The assembly of protein filaments drives many cellular processes, from nucleoid segregation, growth, and division in single cells to muscle contraction in animals. In eukaryotes, shape and motility are regulated through cycles of polymerization and depolymerization of actin cytoskeletal networks. In bacteria, the actin homolog MreB forms filaments that coordinate the cell-wall synthesis machinery to regulate rod-shaped growth and contribute to cellular stiffness through unknown mechanisms. Like actin, MreB is an ATPase and requires ATP to polymerize, and polymerization promotes nucleotide hydrolysis. However, it is unclear whether other similarities exist between MreB and actin because the two proteins share low sequence identity and have distinct cellular roles. Here, we use all-atom molecular dynamics simulations to reveal surprising parallels between MreB and actin structural dynamics. We observe that MreB exhibits actin-like polymerization-dependent structural changes, wherein polymerization induces flattening of MreB subunits, which restructures the nucleotide-binding pocket to favor hydrolysis. MreB filaments exhibited nucleotide-dependent intersubunit bending, with hydrolyzed polymers favoring a straighter conformation. We use steered simulations to demonstrate a coupling between intersubunit bending and the degree of flattening of each subunit, suggesting cooperative bending along a filament. Taken together, our results provide molecular-scale insight into the diversity of structural states of MreB and the relationships among polymerization, hydrolysis, and filament properties, which may be applicable to other members of the broad actin family.

    View details for DOI 10.1073/pnas.1317061111

    View details for PubMedID 24550504

  • Isolation and preparation of bacterial cell walls for Ultra-Performance Liquid Chromatography in press, J Vis Exp. Desmarais, S., Cava, F., de Pedro, M., Huang, K. C.
  • The role of hydrolases in bacterial cell-wall growth. Current opinion in microbiology Lee, T. K., Huang, K. C. 2013; 16 (6): 760-766

    Abstract

    Although hydrolysis is known to be as important as synthesis in the growth and development of the bacterial cell wall, the coupling between these processes is not well understood. Bond cleavage can generate deleterious pores, but may also be required for the incorporation of new material and for the expansion of the wall, highlighting the importance of mechanical forces in interpreting the consequences of hydrolysis in models of growth. Critically, minimal essential subsets of hydrolases have now been identified in several model organisms, enabling the reduction of genetic complexity. Recent studies in Bacillus subtilis have provided evidence for both the presence and absence of coupling between synthesis and hydrolysis during sporulation and elongation, respectively. In this review, we discuss strategies for dissecting the relationship between synthesis and hydrolysis using time-lapse imaging, biophysical measurements of cell-wall architecture, and computational modeling.

    View details for DOI 10.1016/j.mib.2013.08.005

    View details for PubMedID 24035761

  • Dimer Dynamics and Filament Organization of the Bacterial Cell Division Protein FtsA. Journal of molecular biology Hsin, J., Fu, R., Huang, K. C. 2013; 425 (22): 4415-4426

    Abstract

    FtsA is a bacterial actin homolog and one of the core proteins involved in cell division. While previous studies have demonstrated the capability of FtsA to polymerize, little is known about its polymerization state in vivo, or if polymerization is necessary for FtsA function. Given that one function of FtsA is to tether FtsZ filaments to the membrane, in vivo polymerization of FtsA imposes geometric constraints and requires a specific polymer curvature direction. Here we report a series of molecular dynamics simulations probing the structural dynamics of FtsA as a dimer and as a tetrameric single filament. We found that the FtsA polymer exhibits a preferred bending direction that would allow for its placement parallel to FtsZ polymers underneath the cytoplasmic membrane. We also identified key interfacial amino acids that mediate FtsA-FtsA interaction, and propose that some amino acids play more critical roles than others. We performed in silico mutagenesis on FtsA and demonstrated that while a moderate mutation at the polymerization interface does not significantly affect polymer properties such as bending direction and association strength, more drastic mutations change both features and could lead to non-functional FtsA.

    View details for DOI 10.1016/j.jmb.2013.07.016

    View details for PubMedID 23871894

  • Motility Enhancement through Surface Modification Is Sufficient for Cyanobacterial Community Organization during Phototaxis. PLoS computational biology Ursell, T., Chau, R. M., Wisen, S., Bhaya, D., Huang, K. C. 2013; 9 (9)

    Abstract

    The emergent behaviors of communities of genotypically identical cells cannot be easily predicted from the behaviors of individual cells. In many cases, it is thought that direct cell-cell communication plays a critical role in the transition from individual to community behaviors. In the unicellular photosynthetic cyanobacterium Synechocystis sp. PCC 6803, individual cells exhibit light-directed motility ("phototaxis") over surfaces, resulting in the emergence of dynamic spatial organization of multicellular communities. To probe this striking community behavior, we carried out time-lapse video microscopy coupled with quantitative analysis of single-cell dynamics under varying light conditions. These analyses suggest that cells secrete an extracellular substance that modifies the physical properties of the substrate, leading to enhanced motility and the ability for groups of cells to passively guide one another. We developed a biophysical model that demonstrates that this form of indirect, surface-based communication is sufficient to create distinct motile groups whose shape, velocity, and dynamics qualitatively match our experimental observations, even in the absence of direct cellular interactions or changes in single-cell behavior. Our computational analysis of the predicted community behavior, across a matrix of cellular concentrations and light biases, demonstrates that spatial patterning follows robust scaling laws and provides a useful resource for the generation of testable hypotheses regarding phototactic behavior. In addition, we predict that degradation of the surface modification may account for the secondary patterns occasionally observed after the initial formation of a community structure. Taken together, our modeling and experiments provide a framework to show that the emergent spatial organization of phototactic communities requires modification of the substrate, and this form of surface-based communication could provide insight into the behavior of a wide array of biological communities.

    View details for DOI 10.1371/journal.pcbi.1003205

    View details for PubMedID 24039562

  • FtsZ Protofilaments Use a Hinge-Opening Mechanism for Constrictive Force Generation SCIENCE Li, Y., Hsin, J., Zhao, L., Cheng, Y., Shang, W., Huang, K. C., Wang, H., Ye, S. 2013; 341 (6144): 392-395

    Abstract

    The essential bacterial protein FtsZ is a guanosine triphosphatase that self-assembles into a structure at the division site termed the "Z ring". During cytokinesis, the Z ring exerts a constrictive force on the membrane by using the chemical energy of guanosine triphosphate hydrolysis. However, the structural basis of this constriction remains unresolved. Here, we present the crystal structure of a guanosine diphosphate-bound Mycobacterium tuberculosis FtsZ protofilament, which exhibits a curved conformational state. The structure reveals a longitudinal interface that is important for function. The protofilament curvature highlights a hydrolysis-dependent conformational switch at the T3 loop that leads to longitudinal bending between subunits, which could generate sufficient force to drive cytokinesis.

    View details for DOI 10.1126/science.1239248

    View details for Web of Science ID 000322259200048

    View details for PubMedID 23888039

  • Peptidoglycan at its peaks: how chromatographic analyses can reveal bacterial cell wall structure and assembly. Molecular microbiology Desmarais, S. M., de Pedro, M. A., Cava, F., Huang, K. C. 2013; 89 (1): 1-13

    Abstract

    The peptidoglycan (PG) cell wall is a unique macromolecule responsible for both shape determination and cellular integrity under osmotic stress in virtually all bacteria. A quantitative understanding of the relationships between PG architecture, morphogenesis, immune system activation and pathogenesis can provide molecular-scale insights into the function of proteins involved in cell wall synthesis and cell growth. High-performance liquid chromatography (HPLC) has played an important role in our understanding of the structural and chemical complexity of the cell wall by providing an analytical method to quantify differences in chemical composition. Here, we present a primer on the basic chemical features of wall structure that can be revealed through HPLC, along with a description of the applications of HPLC PG analyses for interpreting the effects of genetic and chemical perturbations to a variety of bacterial species in different environments. We describe the physical consequences of different PG compositions on cell shape, and review complementary experimental and computational methodologies for PG analysis. Finally, we present a partial list of future targets of development for HPLC and related techniques.

    View details for DOI 10.1111/mmi.12266

    View details for PubMedID 23679048

  • Optimal Dynamics for Quality Control in Spatially Distributed Mitochondrial Networks PLOS COMPUTATIONAL BIOLOGY Patel, P. K., Shirihai, O., Huang, K. C. 2013; 9 (7)

    Abstract

    Recent imaging studies of mitochondrial dynamics have implicated a cycle of fusion, fission, and autophagy in the quality control of mitochondrial function by selectively increasing the membrane potential of some mitochondria at the expense of the turnover of others. This complex, dynamical system creates spatially distributed networks that are dependent on active transport along cytoskeletal networks and on protein import leading to biogenesis. To study the relative impacts of local interactions between neighboring mitochondria and their reorganization via transport, we have developed a spatiotemporal mathematical model encompassing all of these processes in which we focus on the dynamics of a health parameter meant to mimic the functional state of mitochondria. In agreement with previous models, we show that both autophagy and the generation of membrane potential asymmetry following a fusion/fission cycle are required for maintaining a healthy mitochondrial population. This health maintenance is affected by mitochondrial density and motility primarily through changes in the frequency of fusion events. Health is optimized when the selectivity thresholds for fusion and fission are matched, providing a mechanistic basis for the observed coupling of the two processes through the protein OPA1. We also demonstrate that the discreteness of the components exchanged during fusion is critical for quality control, and that the effects of limiting total amounts of autophagy and biogenesis have distinct consequences on health and population size, respectively. Taken together, our results show that several general principles emerge from the complexity of the quality control cycle that can be used to focus and interpret future experimental studies, and our modeling framework provides a road-map for deconstructing the functional importance of local interactions in communities of cells as well as organelles.

    View details for DOI 10.1371/journal.pcbi.1003108

    View details for Web of Science ID 000322320200003

    View details for PubMedID 23874166

  • Design of High-Specificity Nanocarriers by Exploiting Non-Equilibrium Effects in Cancer Cell Targeting PLOS ONE Tsekouras, K., Goncharenko, I., Colvin, M. E., Huang, K. C., Gopinathan, A. 2013; 8 (6)
  • Mechanical consequences of cell-wall turnover in the elongation of a gram-positive bacterium. Biophysical journal Misra, G., Rojas, E. R., Gopinathan, A., Huang, K. C. 2013; 104 (11): 2342-2352

    Abstract

    A common feature of walled organisms is their exposure to osmotic forces that challenge the mechanical integrity of cells while driving elongation. Most bacteria rely on their cell wall to bear osmotic stress and determine cell shape. Wall thickness can vary greatly among species, with Gram-positive bacteria having a thicker wall than Gram-negative bacteria. How wall dimensions and mechanical properties are regulated and how they affect growth have not yet been elucidated. To investigate the regulation of wall thickness in the rod-shaped Gram-positive bacterium Bacillus subtilis, we analyzed exponentially growing cells in different media. Using transmission electron and epifluorescence microscopy, we found that wall thickness and strain were maintained even between media that yielded a threefold change in growth rate. To probe mechanisms of elongation, we developed a biophysical model of the Gram-positive wall that balances the mechanical effects of synthesis of new material and removal of old material through hydrolysis. Our results suggest that cells can vary their growth rate without changing wall thickness or strain by maintaining a constant ratio of synthesis and hydrolysis rates. Our model also indicates that steady growth requires wall turnover on the same timescale as elongation, which can be driven primarily by hydrolysis rather than insertion. This perspective of turnover-driven elongation provides mechanistic insight into previous experiments involving mutants whose growth rate was accelerated by the addition of lysozyme or autolysin. Our approach provides a general framework for deconstructing shape maintenance in cells with thick walls by integrating wall mechanics with the kinetics and regulation of synthesis and turnover.

    View details for DOI 10.1016/j.bpj.2013.04.047

    View details for PubMedID 23746506

  • Physiological role of FtsA polymerization during bacterial cell division J MolBiol Hsin, J., Fu, R., Huang, K. C. 2013; 425: 4415-4426 
  • The role of hydrolases in bacterial cell-wall growth CurrOpinMicrobiol  Lee, T. K., Huang, K. C. 2013; 16: xx-yy
  • Multiple conformations of FtsZ protofilaments provide structural insight into mechanisms of bacterial cytokinesis Science Li, Y., Hsin, J., Zhao, L., Cheng, Y., Huang, K. C., Wang, H. W. 2013; 341: 392-395
  • Biological Consequences and Advantages of Asymmetric Bacterial Growth ANNUAL REVIEW OF MICROBIOLOGY, VOL 67 Kysela, D. T., Brown, P. J., Huang, K. C., Brun, Y. V. 2013; 67: 417-435

    Abstract

    Asymmetries in cell growth and division occur in eukaryotes and prokaryotes alike. Even seemingly simple and morphologically symmetric cell division processes belie inherent underlying asymmetries in the composition of the resulting daughter cells. We consider the types of asymmetry that arise in various bacterial cell growth and division processes, which include both conditionally activated mechanisms and constitutive, hardwired aspects of bacterial life histories. Although asymmetry disposes some cells to the deleterious effects of aging, it may also benefit populations by efficiently purging accumulated damage and rejuvenating newborn cells. Asymmetries may also generate phenotypic variation required for successful exploitation of variable environments, even when extrinsic changes outpace the capacity of cells to sense and respond to challenges. We propose specific experimental approaches to further develop our understanding of the prevalence and the ultimate importance of asymmetric bacterial growth.

    View details for DOI 10.1146/annurev-micro-092412-155622

    View details for Web of Science ID 000326686400021

    View details for PubMedID 23808335

  • Optimal Nanocarrier Design for Cancer Cell Targeting PloS One Tsekouras, K., Goncharenko, I., Colvin, M., Huang, K. C., Gopinathan, A. 2013; 8: e65623
  • The molecular origins of chiral growth in walled cells CURRENT OPINION IN MICROBIOLOGY Huang, K. C., Ehrhardt, D. W., Shaevitz, J. W. 2012; 15 (6): 707-714

    Abstract

    Cells from all kingdoms of life adopt a dizzying array of fascinating shapes that support cellular function. Amoeboid and spherical shapes represent perhaps the simplest of geometries that may minimize the level of growth control required for survival. Slightly more complex are rod-shaped cells, from microscopic bacteria to macroscopic plants, which require additional mechanisms to define a cell's longitudinal axis, width, and length. Recent evidence suggests that many rod-shaped, walled cells achieve elongated growth through chiral insertion of cell-wall material that may be coupled to a twisting of the cell body. Inspired by these observations, biophysical mechanisms for twisting growth have been proposed that link the mechanics of intracellular proteins to cell shape maintenance. In this review, we highlight experimental and theoretical work that connects molecular-scale organization and structure with the cellular-scale phenomena of rod-shaped growth.

    View details for DOI 10.1016/j.mib.2012.11.002

    View details for Web of Science ID 000313612200012

    View details for PubMedID 23194654

  • Analysis of Surface Protein Expression Reveals the Growth Pattern of the Gram-Negative Outer Membrane PLOS COMPUTATIONAL BIOLOGY Ursell, T. S., Trepagnier, E. H., Huang, K. C., Theriot, J. A. 2012; 8 (9)

    Abstract

    The outer membrane (OM) of Gram-negative bacteria is a complex bilayer composed of proteins, phospholipids, lipoproteins, and lipopolysaccharides. Despite recent advances revealing the molecular pathways underlying protein and lipopolysaccharide incorporation into the OM, the spatial distribution and dynamic regulation of these processes remain poorly understood. Here, we used sequence-specific fluorescent labeling to map the incorporation patterns of an OM-porin protein, LamB, by labeling proteins only after epitope exposure on the cell surface. Newly synthesized LamB appeared in discrete puncta, rather than evenly distributed over the cell surface. Further growth of bacteria after labeling resulted in divergence of labeled LamB puncta, consistent with a spatial pattern of OM growth in which new, unlabeled material was also inserted in patches. At the poles, puncta remained relatively stationary through several rounds of division, a salient characteristic of the OM protein population as a whole. We propose a biophysical model of growth in which patches of new OM material are added in discrete bursts that evolve in time according to Stokes flow and are randomly distributed over the cell surface. Simulations based on this model demonstrate that our experimental observations are consistent with a bursty insertion pattern without spatial bias across the cylindrical cell surface, with approximately one burst of ? 10(-2) µm(2) of OM material per two minutes per µm(2). Growth by insertion of discrete patches suggests that stochasticity plays a major role in patterning and material organization in the OM.

    View details for DOI 10.1371/journal.pcbi.1002680

    View details for Web of Science ID 000309510900017

    View details for PubMedID 23028278

  • Physical constraints on the establishment of intracellular spatial gradients in bacteria BMC BIOPHYSICS Tropini, C., Rabbani, N., Huang, K. C. 2012; 5

    Abstract

    Bacteria dynamically regulate their intricate intracellular organization involving proteins that facilitate cell division, motility, and numerous other processes. Consistent with this sophisticated organization, bacteria are able to create asymmetries and spatial gradients of proteins by localizing signaling pathway components. We use mathematical modeling to investigate the biochemical and physical constraints on the generation of intracellular gradients by the asymmetric localization of a source and a sink.We present a systematic computational analysis of the effects of other regulatory mechanisms, such as synthesis, degradation, saturation, and cell growth. We also demonstrate that gradients can be established in a variety of bacterial morphologies such as rods, crescents, spheres, branched and constricted cells.Taken together, these results suggest that gradients are a robust and potentially common mechanism for providing intracellular spatial cues.

    View details for DOI 10.1186/2046-1682-5-17

    View details for Web of Science ID 000311052500001

    View details for PubMedID 22931750

  • Interplay between the Localization and Kinetics of Phosphorylation in Flagellar Pole Development of the Bacterium Caulobacter crescentus PLOS COMPUTATIONAL BIOLOGY Tropini, C., Huang, K. C. 2012; 8 (8)

    Abstract

    Bacterial cells maintain sophisticated levels of intracellular organization that allow for signal amplification, response to stimuli, cell division, and many other critical processes. The mechanisms underlying localization and their contribution to fitness have been difficult to uncover, due to the often challenging task of creating mutants with systematically perturbed localization but normal enzymatic activity, and the lack of quantitative models through which to interpret subtle phenotypic changes. Focusing on the model bacterium Caulobacter crescentus, which generates two different types of daughter cells from an underlying asymmetric distribution of protein phosphorylation, we use mathematical modeling to investigate the contribution of the localization of histidine kinases to the establishment of cellular asymmetry and subsequent developmental outcomes. We use existing mutant phenotypes and fluorescence data to parameterize a reaction-diffusion model of the kinases PleC and DivJ and their cognate response regulator DivK. We then present a systematic computational analysis of the effects of changes in protein localization and abundance to determine whether PleC localization is required for correct developmental timing in Caulobacter. Our model predicts the developmental phenotypes of several localization mutants, and suggests that a novel strain with co-localization of PleC and DivJ could provide quantitative insight into the signaling threshold required for flagellar pole development. Our analysis indicates that normal development can be maintained through a wide range of localization phenotypes, and that developmental defects due to changes in PleC localization can be rescued by increased PleC expression. We also show that the system is remarkably robust to perturbation of the kinetic parameters, and while the localization of either PleC or DivJ is required for asymmetric development, the delocalization of one of these two components does not prevent flagellar pole development. We further find that allosteric regulation of PleC observed in vitro does not affect the predicted in vivo developmental phenotypes. Taken together, our model suggests that cells can tolerate perturbations to localization phenotypes, whose evolutionary origins may be connected with reducing protein expression or with decoupling pre- and post-division phenotypes.

    View details for DOI 10.1371/journal.pcbi.1002602

    View details for Web of Science ID 000308553500004

    View details for PubMedID 22876167

  • Posttranslational Acetylation of alpha-Tubulin Constrains Protofilament Number in Native Microtubules CURRENT BIOLOGY Cueva, J. G., Hsin, J., Huang, K. C., Goodman, M. B. 2012; 22 (12): 1066-1074

    Abstract

    Microtubules are built from linear polymers of ?-? tubulin dimers (protofilaments) that form a tubular quinary structure. Microtubules assembled from purified tubulin in vitro contain between 10 and 16 protofilaments; however, such structural polymorphisms are not found in cells. This discrepancy implies that factors other than tubulin constrain microtubule protofilament number, but the nature of these constraints is unknown.Here, we show that acetylation of MEC-12 ?-tubulin constrains protofilament number in C. elegans touch receptor neurons (TRNs). Whereas the sensory dendrite of wild-type TRNs is packed with a cross-linked bundle of long, 15-protofilament microtubules, mec-17;atat-2 mutants lacking ?-tubulin acetyltransferase activity have short microtubules, rampant lattice defects, and variable protofilament number both between and within microtubules. All-atom molecular dynamics simulations suggest a model in which acetylation of lysine 40 promotes the formation of interprotofilament salt bridges, stabilizing lateral interactions between protofilaments and constraining quinary structure to produce stable, structurally uniform microtubules in vivo.Acetylation of ?-tubulin is an essential constraint on protofilament number in vivo. We propose a structural model in which this posttranslational modification promotes the formation of lateral salt bridges that fine-tune the association between adjacent protofilaments and enable the formation of uniform microtubule populations in vivo.

    View details for DOI 10.1016/j.cub.2012.05.012

    View details for Web of Science ID 000305766900020

    View details for PubMedID 22658592

  • Nucleotide-dependent conformations of FtsZ dimers and force generation observed through molecular dynamics simulations PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Hsin, J., Gopinathan, A., Huang, K. C. 2012; 109 (24): 9432-9437

    Abstract

    The bacterial cytoskeletal protein FtsZ is a GTPase that is thought to provide mechanical constriction force via an unidentified mechanism. Purified FtsZ polymerizes into filaments with varying structures in vitro: while GTP-bound FtsZ assembles into straight or gently curved filaments, GDP-bound FtsZ forms highly curved filaments, prompting the hypothesis that a difference in the inherent curvature of FtsZ filaments provides mechanical force. However, no nucleotide-dependent structural transition of FtsZ monomers has been observed to support this force generation model. Here, we present a series of all-atom molecular dynamics simulations probing the effects of nucleotide binding on the structure of an FtsZ dimer. We found that the FtsZ-dimer structure is dependent on nucleotide-binding state. While a GTP-bound FtsZ dimer retained a firm monomer-monomer contact, a GDP-bound FtsZ dimer lost some of the monomer-monomer association, leading to a "hinge-opening" event that resulted in a more bent dimer, while leaving each monomer structure largely unaffected. We constructed models of FtsZ filaments and found that a GDP-FtsZ filament is much more curved than a GTP-FtsZ filament, with the degree of curvature matching prior experimental data. FtsZ dynamics were used to estimate the amount of force an FtsZ filament could exert when hydrolysis occurs (20-30 pN per monomer). This magnitude of force is sufficient to direct inward cell-wall growth during division, and to produce the observed degree of membrane pinching in liposomes. Taken together, our data provide molecular-scale insight on the origin of FtsZ-based constriction force, and the mechanism underlying prokaryotic cell division.

    View details for DOI 10.1073/pnas.1120761109

    View details for Web of Science ID 000305511300049

    View details for PubMedID 22647609

  • Measuring the stiffness of bacterial cells from growth rates in hydrogels of tunable elasticity MOLECULAR MICROBIOLOGY Tuson, H. H., Auer, G. K., Renner, L. D., Hasebe, M., Tropini, C., Salick, M., Crone, W. C., Gopinathan, A., Huang, K. C., Weibel, D. B. 2012; 84 (5): 874-891

    Abstract

    Although bacterial cells are known to experience large forces from osmotic pressure differences and their local microenvironment, quantitative measurements of the mechanical properties of growing bacterial cells have been limited. We provide an experimental approach and theoretical framework for measuring the mechanical properties of live bacteria. We encapsulated bacteria in agarose with a user-defined stiffness, measured the growth rate of individual cells and fit data to a thin-shell mechanical model to extract the effective longitudinal Young's modulus of the cell envelope of Escherichia coli (50-150 MPa), Bacillus subtilis (100-200 MPa) and Pseudomonas aeruginosa (100-200 MPa). Our data provide estimates of cell wall stiffness similar to values obtained via the more labour-intensive technique of atomic force microscopy. To address physiological perturbations that produce changes in cellular mechanical properties, we tested the effect of A22-induced MreB depolymerization on the stiffness of E. coli. The effective longitudinal Young's modulus was not significantly affected by A22 treatment at short time scales, supporting a model in which the interactions between MreB and the cell wall persist on the same time scale as growth. Our technique therefore enables the rapid determination of how changes in genotype and biochemistry affect the mechanical properties of the bacterial envelope.

    View details for DOI 10.1111/j.1365-2958.2012.08063.x

    View details for Web of Science ID 000304301500007

    View details for PubMedID 22548341

  • Helical insertion of peptidoglycan produces chiral ordering of the bacterial cell wall PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Wang, S., Furchtgott, L., Huang, K. C., Shaevitz, J. W. 2012; 109 (10): E595-E604

    Abstract

    The regulation of cell shape is a common challenge faced by organisms across all biological kingdoms. In nearly all bacteria, cell shape is determined by the architecture of the peptidoglycan cell wall, a macromolecule consisting of glycan strands crosslinked by peptides. In addition to shape, cell growth must also maintain the wall structural integrity to prevent lysis due to large turgor pressures. Robustness can be accomplished by establishing a globally ordered cell-wall network, although how a bacterium generates and maintains peptidoglycan order on the micron scale using nanometer-sized proteins remains a mystery. Here, we demonstrate that left-handed chirality of the MreB cytoskeleton in the rod-shaped bacterium Escherichia coli gives rise to a global, right-handed chiral ordering of the cell wall. Local, MreB-guided insertion of material into the peptidoglycan network naturally orders the glycan strands and causes cells to twist left-handedly during elongational growth. Through comparison with the right-handed twisting of Bacillus subtilis cells, our work supports a common mechanism linking helical insertion and chiral cell-wall ordering in rod-shaped bacteria. These physical principles of cell growth link the molecular structure of the bacterial cytoskeleton, mechanisms of wall synthesis, and the coordination of cell-wall architecture.

    View details for DOI 10.1073/pnas.1117132109

    View details for Web of Science ID 000301117700005

    View details for PubMedID 22343529

  • Alpha Tubulin Acetylation Regulates Protofilament Number in Native Microtubules Curr Biol Cueva, J., Hsin, J., Huang, K. C., Goodman, M. 2012; 22: 1066-1074
  • Conformational changes, diffusion and collective behavior in monomeric kinesin-based motility JOURNAL OF PHYSICS-CONDENSED MATTER Huang, K. C., Vega, C., Gopinathan, A. 2011; 23 (37)

    Abstract

    Molecular motors convert chemical energy into mechanical motion and power the transport of material within living cells; the motion of a motor is thought to be influenced by stochastic chemical state transitions of the molecule as well as intramolecular diffusion of one motor head seeking the next binding site. Existing models for the motility of single-headed monomeric motors that map the system to a simplified two-state Brownian ratchet have some predictive power, but in general are unable to elucidate the contributions of different molecular level processes to the overall effective parameters. In this work, we build a detailed molecular level model of monomeric kinesin motility that naturally incorporates conformational changes (power strokes) and biased diffusion. Our results predict that mean velocity is most sensitive to the power stroke size, while run length distribution is sensitive primarily to the strength of the microtubule bias potential with a weak dependence on power stroke that can be tuned by the strength of an applied load. In addition, we demonstrate that motor pairs attached to the same cargo can cooperatively function to increase motility in both the plus- and minus-end directions. These findings illustrate the importance of a detailed mechanochemical model for dissecting the contributions of microscopic parameters to monomeric kinesin dynamics.

    View details for DOI 10.1088/0953-8984/23/37/374106

    View details for Web of Science ID 000294785400007

    View details for PubMedID 21862841

  • The bacterial actin MreB rotates, and rotation depends on cell-wall assembly PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA van Teeffelen, S., Wang, S., Furchtgott, L., Huang, K. C., Wingreen, N. S., Shaevitz, J. W., Gitai, Z. 2011; 108 (38): 15822-15827

    Abstract

    Bacterial cells possess multiple cytoskeletal proteins involved in a wide range of cellular processes. These cytoskeletal proteins are dynamic, but the driving forces and cellular functions of these dynamics remain poorly understood. Eukaryotic cytoskeletal dynamics are often driven by motor proteins, but in bacteria no motors that drive cytoskeletal motion have been identified to date. Here, we quantitatively study the dynamics of the Escherichia coli actin homolog MreB, which is essential for the maintenance of rod-like cell shape in bacteria. We find that MreB rotates around the long axis of the cell in a persistent manner. Whereas previous studies have suggested that MreB dynamics are driven by its own polymerization, we show that MreB rotation does not depend on its own polymerization but rather requires the assembly of the peptidoglycan cell wall. The cell-wall synthesis machinery thus either constitutes a novel type of extracellular motor that exerts force on cytoplasmic MreB, or is indirectly required for an as-yet-unidentified motor. Biophysical simulations suggest that one function of MreB rotation is to ensure a uniform distribution of new peptidoglycan insertion sites, a necessary condition to maintain rod shape during growth. These findings both broaden the view of cytoskeletal motors and deepen our understanding of the physical basis of bacterial morphogenesis.

    View details for DOI 10.1073/pnas.1108999108

    View details for Web of Science ID 000295030000036

    View details for PubMedID 21903929

  • Does the Potential for Chaos Constrain the Embryonic Cell-Cycle Oscillator? PLOS COMPUTATIONAL BIOLOGY McIsaac, R. S., Huang, K. C., Sengupta, A., Wingreen, N. S. 2011; 7 (7)

    Abstract

    Although many of the core components of the embryonic cell-cycle network have been elucidated, the question of how embryos achieve robust, synchronous cellular divisions post-fertilization remains unexplored. What are the different schemes that could be implemented by the embryo to achieve synchronization? By extending a cell-cycle model previously developed for embryos of the frog Xenopus laevis to include the spatial dimensions of the embryo, we establish a novel role for the rapid, fertilization-initiated calcium wave that triggers cell-cycle oscillations. Specifically, in our simulations a fast calcium wave results in synchronized cell cycles, while a slow wave results in full-blown spatio-temporal chaos. We show that such chaos would ultimately lead to an unpredictable patchwork of cell divisions across the embryo. Given this potential for chaos, our results indicate a novel design principle whereby the fast calcium-wave trigger following embryo fertilization synchronizes cell divisions.

    View details for DOI 10.1371/journal.pcbi.1002109

    View details for Web of Science ID 000293333200014

    View details for PubMedID 21779158

  • Mechanisms for maintaining cell shape in rod-shaped Gram-negative bacteria MOLECULAR MICROBIOLOGY Furchtgott, L., Wingreen, N. S., Huang, K. C. 2011; 81 (2): 340-353

    Abstract

    For the rod-shaped Gram-negative bacterium Escherichia coli, changes in cell shape have critical consequences for motility, immune system evasion, proliferation and adhesion. For most bacteria, the peptidoglycan cell wall is both necessary and sufficient to determine cell shape. However, how the synthesis machinery assembles a peptidoglycan network with a robustly maintained micron-scale shape has remained elusive. To explore shape maintenance, we have quantified the robustness of cell shape in three Gram-negative bacteria in different genetic backgrounds and in the presence of an antibiotic that inhibits division. Building on previous modelling suggesting a prominent role for mechanical forces in shape regulation, we introduce a biophysical model for the growth dynamics of rod-shaped cells to investigate the roles of spatial regulation of peptidoglycan synthesis, glycan-strand biochemistry and mechanical stretching during insertion. Our studies reveal that rod-shape maintenance requires insertion to be insensitive to fluctuations in cell-wall density and stress, and even a simple helical pattern of insertion is sufficient for over sixfold elongation without significant loss in shape. In addition, we demonstrate that both the length and pre-stretching of newly inserted strands regulate cell width. In sum, we show that simple physical rules can allow bacteria to achieve robust, shape-preserving cell-wall growth.

    View details for DOI 10.1111/j.1365-2958.2011.07616.x

    View details for Web of Science ID 000292567200007

    View details for PubMedID 21501250

  • Mechanics of membrane bulging during cell-wall disruption in Gram-negative bacteria PHYSICAL REVIEW E Daly, K. E., Huang, K. C., Wingreen, N. S., Mukhopadhyay, R. 2011; 83 (4)

    Abstract

    The bacterial cell wall is a network of sugar strands crosslinked by peptides that serve as the primary structure for bearing osmotic stress. Despite its importance in cellular survival, the robustness of the cell wall to network defects has been relatively unexplored. Treatment of the gram-negative bacterium Escherichia coli with the antibiotic vancomycin, which disrupts the crosslinking of new material during growth, leads to the development of pronounced bulges and eventually of cell lysis. Here, we model the mechanics of the bulging of the cytoplasmic membrane through pores in the cell wall. We find that the membrane undergoes a transition between a nearly flat state and a spherical bulge at a critical pore radius of ~20 nm. This critical pore size is large compared to the typical distance between neighboring peptides and glycan strands, and hence pore size acts as a constraint on network integrity. We also discuss the general implications of our model to membrane deformations in eukaryotic blebbing and vesiculation in red blood cells.

    View details for DOI 10.1103/PhysRevE.83.041922

    View details for Web of Science ID 000290152800013

    View details for PubMedID 21599215

  • Bilayer-Mediated Clustering and Functional Interaction of MscL Channels BIOPHYSICAL JOURNAL Grage, S. L., Keleshian, A. M., Turdzeladze, T., Battle, A. R., Tay, W. C., May, R. P., Holt, S. A., Contera, S. A., Haertlein, M., Moulin, M., Pal, P., Rohde, P. R., Forsyth, V. T., Watts, A., Huang, K. C., Ulrich, A. S., Martinac, B. 2011; 100 (5): 1252-1260

    Abstract

    Mechanosensitive channels allow bacteria to respond to osmotic stress by opening a nanometer-sized pore in the cellular membrane. Although the underlying mechanism has been thoroughly studied on the basis of individual channels, the behavior of channel ensembles has yet to be elucidated. This work reveals that mechanosensitive channels of large conductance (MscL) exhibit a tendency to spatially cluster, and demonstrates the functional relevance of clustering. We evaluated the spatial distribution of channels in a lipid bilayer using patch-clamp electrophysiology, fluorescence and atomic force microscopy, and neutron scattering and reflection techniques, coupled with mathematical modeling of the mechanics of a membrane crowded with proteins. The results indicate that MscL forms clusters under a wide range of conditions. MscL is closely packed within each cluster but is still active and mechanosensitive. However, the channel activity is modulated by the presence of neighboring proteins, indicating membrane-mediated protein-protein interactions. Collectively, these results suggest that MscL self-assembly into channel clusters plays an osmoregulatory functional role in the membrane.

    View details for DOI 10.1016/j.bpj.2011.01.023

    View details for Web of Science ID 000288049400013

    View details for PubMedID 21354398

  • Spatial gradient of protein phosphorylation underlies replicative asymmetry in a bacterium PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Chen, Y. E., Tropini, C., Jonas, K., Tsokos, C. G., Huang, K. C., Laub, M. T. 2011; 108 (3): 1052-1057

    Abstract

    Spatial asymmetry is crucial to development. One mechanism for generating asymmetry involves the localized synthesis of a key regulatory protein that diffuses away from its source, forming a spatial gradient. Although gradients are prevalent in eukaryotes, at both the tissue and intracellular levels, it is unclear whether gradients of freely diffusible proteins can form within bacterial cells given their small size and the speed of diffusion. Here, we show that the bacterium Caulobacter crescentus generates a gradient of the active, phosphorylated form of the master regulator CtrA, which directly regulates DNA replication. Using a combination of mathematical modeling, single-cell microscopy, and genetic manipulation, we demonstrate that this gradient is produced by the polarly localized phosphorylation and dephosphorylation of CtrA. Our data indicate that cells robustly establish the asymmetric fates of daughter cells before cell division causes physical compartmentalization. More generally, our results demonstrate that uniform protein abundance may belie gradients and other sophisticated spatial patterns of protein activity in bacterial cells.

    View details for DOI 10.1073/pnas.1015397108

    View details for Web of Science ID 000286310300033

    View details for PubMedID 21191097

  • The mechanics of membrane bulging during cell-wall disruption in Gram-negative bacteria Phys. Rev. Selected for May 1, 2011 issue of Virtual Journal of Biological Physics Research. Daly, K. E., Huang, K. C., Wingreen, N. S., Mukhopadhyay, R. 2011; 83: 041922
  • Resolution limits of optical microscopy and the mind Biomed Comp Rev Usrell, T. S., Huang, K. C. 2011; 7: 27
  • Clustering and functional interaction of MscL channels Biophys. J. Grage, L., Keleshian, A. M., Turdzeladze, T., Battle, A. R., Tay, W. C., May, R. P., Huang, K. 2011; 100: 1252-1260
  • A spatial gradient of protein phosphorylation underlies replicative asymmetry in a bacterium Proc Nat Acadsci USA. Selected for Feb 1, 2011 issue of Virtual Journal of Biological Physics Research. Chen, Y. E., Tropini, C., Huang, K. C., Laub, M. T. 2011; 108: 1052-1057
  • Dynamic SpoIIIE assembly mediates septal membrane fission during Bacillus subtilis sporulation GENES & DEVELOPMENT Fleming, T. C., Shin, J. Y., Lee, S., Becker, E., Huang, K. C., Bustamante, C., Pogliano, K. 2010; 24 (11): 1160-1172

    Abstract

    SpoIIIE is an FtsK-related protein that transports the forespore chromosome across the Bacillus subtilis sporulation septum. We use membrane photobleaching and protoplast assays to demonstrate that SpoIIIE is required for septal membrane fission in the presence of trapped DNA, and that DNA is transported across separate daughter cell membranes, suggesting that SpoIIIE forms a channel that partitions the daughter cell membranes. Our results reveal a close correlation between septal membrane fission and the assembly of a stable SpoIIIE translocation complex at the septal midpoint. Time-lapse epifluorescence, total internal reflection fluorescence (TIRF) microscopy, and live-cell photoactivation localization microscopy (PALM) demonstrate that the SpoIIIE transmembrane domain mediates dynamic localization to active division sites, whereas the assembly of a stable focus also requires the cytoplasmic domain. The transmembrane domain fails to completely separate the membrane, and it assembles unstable foci. TIRF microscopy and biophysical modeling of fluorescence recovery after photobleaching (FRAP) data suggest that this unstable protein transitions between disassembled and assembled oligomeric states. We propose a new model for the role of SpoIIIE assembly in septal membrane fission that has strong implications for how the chromosome terminus crosses the septum.

    View details for DOI 10.1101/gad.1925210

    View details for Web of Science ID 000278267200010

    View details for PubMedID 20516200

  • Macromolecules that prefer their membranes curvy MOLECULAR MICROBIOLOGY Huang, K. C., Ramamurthi, K. S. 2010; 76 (4): 822-832

    Abstract

    Understanding the mechanisms that underlie the organization of bacterial cells has become a significant challenge in the field of bacterial cytology. Of specific interest are early macromolecular sorting events that establish cellular non-uniformity and provide chemical landmarks for later localization events. In this review, we will examine specific examples of lipids and proteins that appear to exploit differences in membrane curvature to drive their localization to particular regions of a bacterial cell. We will also discuss the physical limits of curvature-mediated localization within bacteria, and the use of modelling to infer biophysical properties of curvature-sensing macromolecules.

    View details for DOI 10.1111/j.1365-2958.2010.07168.x

    View details for Web of Science ID 000277607600004

    View details for PubMedID 20444099

  • SpoIIIE assembly mediates septal membrane fission during Bacillus subtilis sporulation Genes and Development  Fleming, T., Becker, E., Lee, S., Shin, J. Y., Huang, K. C., Bustamante, C. 2010; 24: 1160
  • Cell shape and cell-wall organization in Gram-negative bacteria PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Huang, K. C., Mukhopadhyay, R., Wen, B., Gitai, Z., Wingreen, N. S. 2008; 105 (49): 19282-19287

    Abstract

    In bacterial cells, the peptidoglycan cell wall is the stress-bearing structure that dictates cell shape. Although many molecular details of the composition and assembly of cell-wall components are known, how the network of peptidoglycan subunits is organized to give the cell shape during normal growth and how it is reorganized in response to damage or environmental forces have been relatively unexplored. In this work, we introduce a quantitative physical model of the bacterial cell wall that predicts the mechanical response of cell shape to peptidoglycan damage and perturbation in the rod-shaped Gram-negative bacterium Escherichia coli. To test these predictions, we use time-lapse imaging experiments to show that damage often manifests as a bulge on the sidewall, coupled to large-scale bending of the cylindrical cell wall around the bulge. Our physical model also suggests a surprising robustness of cell shape to peptidoglycan defects, helping explain the observed porosity of the cell wall and the ability of cells to grow and maintain their shape even under conditions that limit peptide crosslinking. Finally, we show that many common bacterial cell shapes can be realized within the same model via simple spatial patterning of peptidoglycan defects, suggesting that minor patterning changes could underlie the great diversity of shapes observed in the bacterial kingdom.

    View details for DOI 10.1073/pnas.0805309105

    View details for Web of Science ID 000261706600048

    View details for PubMedID 19050072

  • Lipid localization in bacterial cells through curvature-mediated microphase separation BIOPHYSICAL JOURNAL Mukhopadhyay, R., Huang, K. C., Wingreen, N. S. 2008; 95 (3): 1034-1049

    Abstract

    Although many proteins are known to localize in bacterial cells, for the most part our understanding of how such localization takes place is limited. Recent evidence that the phospholipid cardiolipin localizes to the poles of rod-shaped bacteria suggests that targeting of some proteins may rely on the heterogeneous distribution of membrane lipids. Membrane curvature has been proposed as a factor in the polar localization of high-intrinsic-curvature lipids, but the small size of lipids compared to the dimensions of the cell means that single molecules cannot stably localize. At the other extreme, phase separation of the membrane energetically favors a single domain of such lipids at one pole. We have proposed a physical mechanism in which osmotic pinning of the membrane to the cell wall naturally produces microphase separation, i.e., lipid domains of finite size, whose aggregate sensitivity to cell curvature can support spontaneous and stable localization to both poles. Here, we demonstrate that variations in the strength of pinning of the membrane to the cell wall can also act as a strong localization mechanism, in agreement with observations of cardiolipin relocalization from the poles to the septum during sporulation in the bacterium Bacillus subtilis. In addition, we rigorously determine the relationship between localization and the domain-size distribution including the effects of entropy, and quantify the strength of domain-domain interactions. Our model predicts a critical concentration of cardiolipin below which domains will not form and hence polar localization will not take place. This observation is consistent with recent experiments showing that in Escherichia coli cells with reduced cardiolipin concentrations, cardiolipin and the osmoregulatory protein ProP fail to localize to the poles.

    View details for DOI 10.1529/biophysj.107.126920

    View details for Web of Science ID 000257719200005

    View details for PubMedID 18390605

  • The Min system as a general cell-geometry detection mechanism: patterns of Min oscillations respond to changes in cell shape in aberrantly shaped Escherichia coli J. Bacteriol Varma, A., Huang, K. C., Young, K. D. 2008; 190: 2106
  • Cooperative gating and spatial organization of membrane proteins through elastic interactions PLoS Comp. Biol. Ursell, T., Huang, K. C., Peterson, E., Phillips, R. 2007; 3: e81
  • A curvature-mediated mechanism for localization of lipids to bacterial poles PLOS COMPUTATIONAL BIOLOGY Huang, K. C., Mukhopadhyay, R., Wingreen, N. S. 2006; 2 (11): 1357-1364

    Abstract

    Subcellular protein localization is a universal feature of eukaryotic cells, and the ubiquity of protein localization in prokaryotic species is now acquiring greater appreciation. Though some targeting anchors are known, the origin of polar and division-site localization remains mysterious for a large fraction of bacterial proteins. Ultimately, the molecular components responsible for such symmetry breaking must employ a high degree of self-organization. Here we propose a novel physical mechanism, based on the two-dimensional curvature of the membrane, for spontaneous lipid targeting to the poles and division site of rod-shaped bacterial cells. If one of the membrane components has a large intrinsic curvature, the geometrical constraint of the plasma membrane by the more rigid bacterial cell wall naturally leads to lipid microphase separation. We find that the resulting clusters of high-curvature lipids are large enough to spontaneously and stably localize to the two cell poles. Recent evidence of localization of the phospholipid cardiolipin to the poles of bacterial cells suggests that polar targeting of some proteins may rely on the membrane's differential lipid content. More generally, aggregates of lipids, proteins, or lipid-protein complexes may localize in response to features of cell geometry incapable of localizing individual molecules.

    View details for DOI 10.1371/journal.pcbi.0020151

    View details for Web of Science ID 000242375200005

    View details for PubMedID 17096591

  • Nanoscale properties of melting at the surface of semiconductors PHYSICAL REVIEW B Huang, K. C., Wang, T., Joannopoulos, J. D. 2005; 72 (19)
  • Superheating and induced melting at semiconductor interfaces PHYSICAL REVIEW LETTERS Huang, K. C., Wang, T., Joannopoulos, J. D. 2005; 94 (17)

    Abstract

    We present ab initio density-functional simulations of the state of several semiconductor surfaces at temperatures near the bulk melting temperatures. We find that the solid-liquid phase-transition temperature at the surface can be altered via a microscopic (single-monolayer) coating with a different lattice-matched semiconducting material. Our results show that a single-monolayer GaAs coating on a Ge(110) surface above the Ge melting temperature can dramatically reduce the diffusion coefficient of the germanium atoms, going so far as to prevent melting of the bulk layers on the 10 ps time scale. In contrast, a single-monolayer coating of Ge on a GaAs(110) surface introduces defects into the bulk and induces melting of the top layer of GaAs atoms 300 K below the GaAs melting point. To our knowledge, these calculations represent the first ab initio investigation of the superheating and induced melting phenomena.

    View details for DOI 10.1103/PhysRevLett.94.175702

    View details for Web of Science ID 000228932200044

    View details for PubMedID 15904312

  • Photonic Band-Gaps and Localization in the Thue-Morse Structures Appl. Phys. Lett. Selected for May 23, 2005 issue of Virtual Journal of Nanoscale Science & Technology. Jiang, X., Zhang, Y., Feng, S., Huang, K. C., Yi, Y., Joannopoulos, J. D. 2005; 86: 201110
  • Min-protein oscillations in round bacteria. Physical biology Huang, K. C., Wingreen, N. S. 2004; 1 (3-4): 229-235

    Abstract

    In rod-shaped Escherichia coli cells, the Min proteins, which are involved in division-site selection, oscillate from pole-to-pole. The homologs of the Min proteins from the round bacterium Neisseria gonorrhoeae also form a spatial oscillator when expressed in wild-type and round, rodA- mutants of E. coli, suggesting that the Min proteins form an oscillator in N. gonorrhoeae. Here we report that a numerical model for Min-protein oscillations in rod-shaped cells also produces oscillations in round cells (cocci). Our numerical results explain why the MinE-protein rings found in wild-type E. coli are absent in round mutants. In addition, we find that for round cells there is a minimum radius below which oscillations do not occur, and a maximum radius above which oscillations become mislocalized. Finally, we demonstrate that Min-protein oscillations can select the long axis in nearly round cells based solely on geometry, a potentially important factor in division-plane selection in cocci.

    View details for PubMedID 16204843

  • Negative effective permeability in polaritonic photonic crystals APPLIED PHYSICS LETTERS Huang, K. C., Povinelli, M. L., Joannopoulos, J. D. 2004; 85 (4): 543-545

    View details for DOI 10.1063/1.1775291

    View details for Web of Science ID 000222855400011

  • Nature of lossy Bloch states in polaritonic photonic crystals PHYSICAL REVIEW B Huang, K. C., Lidorikis, E., Jiang, X. Y., Joannopoulos, J. D., Nelson, K. A., Bienstman, P., Fan, S. H. 2004; 69 (19)
  • Pattern Formation within Escherichia coli: Diffusion, Membrane Attachment, and Self-Interaction of MinD Molecules Phys. Rev. Lett. Selected for December 1, 2004 issue of Virtual Journal of Biological Physics. Kulkarni, R. V., Huang, K. C., Kloster, M., Wingreen, N. S. 2004; 93: 228103
  • The nature of lossy Bloch states in polaritonic photonic crystals Phys. Rev. Selected for June 7, 2004 issue of Virtual Journal of Nanoscale Science & Technology. Huang, K. C., Lidorikis, E., Jiang, X., Joannopoulos, J. D., Nelson, K. A., Bienstman, P. 2004; B 69: 195111
  • Dynamic structures in Escherichia coli: Spontaneous formation of MinE rings and MinD polar zones PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Huang, K. C., Meir, Y., Wingreen, N. S. 2003; 100 (22): 12724-12728

    Abstract

    In Escherichia coli, division site selection is regulated in part by the Min-protein system. Oscillations of the Min proteins from pole to pole every approximately 40 sec have been revealed by in vivo studies of GFP fusions. The dynamic oscillatory structures produced by the Min proteins, including a ring of MinE protein, compact polar zones of MinD, and zebra-striped oscillations in filamentous cells, remain unexplained. We show that the Min oscillations, including mutant phenotypes, can be accounted for by in vitro-observed interactions involving MinD and MinE, with a crucial role played by the rate of nucleotide exchange. Recent discoveries suggest that protein oscillations may play a general role in proper chromosome and plasmid partitioning.

    View details for DOI 10.1073/pnas.2135445100

    View details for Web of Science ID 000186301100040

    View details for PubMedID 14569005

  • Phonon-polariton excitations in photonic crystals PHYSICAL REVIEW B Huang, K. C., Bienstman, P., Joannopoulos, J. D., Nelson, K. A., Fan, S. 2003; 68 (7)
  • Field expulsion and reconfiguration in polaritonic photonic crystals PHYSICAL REVIEW LETTERS Huang, K. C., Bienstman, P., Joannopoulos, J. D., Nelson, K. A., Fan, S. H. 2003; 90 (19)

    Abstract

    We uncover a rich set of optical phenomena stemming from the incorporation of polar materials exhibiting transverse phonon polariton excitations into a photonic crystal structure. We identify in the frequency spectrum two regimes in which the dielectric response of the polaritonic medium can induce extreme localization of the electromagnetic energy. Our analysis of the effect of polarization and the interaction between the polariton and photonic band gaps on the Bloch states leads to a pair of mechanisms for sensitive frequency-controlled relocation and/or reconfiguration of the fields.

    View details for DOI 10.1103/PhysRevLett.90.196402

    View details for Web of Science ID 000182928300030

    View details for PubMedID 12785962

  • Comment on "Quantum Monte Carlo study of the dipole moment of CO" J. Chem. Phys. Huang, K. C., Needs, R. J., Rajagopal, G. 1999, 2000; 110, 112: 11700, 4419

Conference Proceedings


  • Mechanisms for Maintaining Cell-Shape in Rod-Shaped Gram-Negative Bacteria Furchtgott, L., Wingreen, N. S., Huang, K. C. CELL PRESS. 2011: 514-514
  • Entropy-driven translocation of an unstructured protein through the Gram-positive cell wall. Halladin, D. K., Huang, K. C., Gopinathan, A., Theriot, J. A. AMER SOC CELL BIOLOGY. 2011
  • Control of melting using nanoscale coatings Huang, K. C., Wang, T., Joannopoulos, J. D. 2007