Bulletin of the American Physical Society
2008 APS March Meeting
Volume 53, Number 2
Monday–Friday, March 10–14, 2008; New Orleans, Louisiana
Session X40: Self Assembled Protein Cages |
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Sponsoring Units: DBP Chair: William Klug, University of California, Los Angeles Room: Morial Convention Center 232 |
Friday, March 14, 2008 8:00AM - 8:12AM |
X40.00001: A minimal model for protein coat dynamics in intracellular vesicular transport Ranjan Mukhopadhyay, Hui Wang, Greg Huber Within eukaryotic cells, proteins are transported by vesicles formed from coated regions of membranes. The assembly of coat proteins deforms the membrane patch and drives vesicle formation. Once the vesicle has pinched off, the protein coat rapidly disassembles. Motivated by recent experimental results, we propose a minimal model for the dynamics of coat assembly and disassembly and study the spatio-temporal behavior of the system. We will show that for a range of parameters, our model can robustly generate a steady state distribution of protein clusters with characteristic sizes and will obtain the scaling behavior of average cluster size with the parameters of the model. We will also discuss the coupling of coat dynamics to sorting of cargo proteins. [Preview Abstract] |
Friday, March 14, 2008 8:12AM - 8:24AM |
X40.00002: The study of viral assembly with fluorescence fluctuation spectroscopy Joachim Mueller, Bin Wu, Yan Chen Enveloped viruses contain an encapsulating membrane that the virus acquires from the host cell during the budding process. The presence of the enveloping lipid membrane complicates the physical characterization of the proteins assembled within the virus considerably. Here we present a method based on fluorescence fluctuations that quantifies the copy number of proteins within an enveloped viral particles. We choose the viral protein Gag of the human immunodeficiency virus (HIV) type 1 as a model system, because Gag expressed in cells is sufficient to produce viral-like particles (VLPs) of the same size as authentic virions. VLPs harvested from cells that express fluorescently labeled Gag were investigated by two-photon fluorescence fluctuation spectroscopy. The autocorrelation functions of the fluctuations revealed a hydrodynamic size of the fluorescent VLPs consistent with previous results based on electron microscopy. Further analysis of the fluctuations revealed a copy number of Gag per virion that is inconsistent with the prevailing model of HIV assembly. We will discuss the implications of our experimental results for the assembly process of VLPs. [Preview Abstract] |
Friday, March 14, 2008 8:24AM - 8:36AM |
X40.00003: Spherical Proteins and Viral Capsids Studied by Theory of Elasticity Zheng Yang, Ivet Bahar, Michael Widom Coarse-grained elastic network models have been successful in elucidating the fluctuation dynamics of proteins around their native conformations. It is well established that the low-frequency collective motions derived by simplified normal mode analysis depend on the overall 3-dimensional shape of the biomolecule. Given that the large scale collective motions are usually involved in biological function, our objective in this work is to gain more insights into large scale collective motions of spherical proteins and virus capsids by considering a continuous model with perfect spherical symmetry. To this end, we compare the global dynamics of proteins and the analytical solutions from an elastic wave equation with spherical boundary conditions. In addition, an icosahedral discrete model is generated and analyzed for validating our continuous model. Applications to lumazine synthase, satellite tobacco mosaic virus and other viruses shows that the spherical elastic model can efficiently provide insights on collective motions that are otherwise obtained by detailed elastic network models. [Preview Abstract] |
Friday, March 14, 2008 8:36AM - 8:48AM |
X40.00004: Low frequency mechanical modes of viruses with atomic detail Eric Dykeman, Otto Sankey The low frequency mechanical modes of viruses can provide important insights into the large global motions that a virus may exhibit. Recently it has been proposed that these large global motions may be excited using impulsive stimulated Raman scattering producing permanent damage to the virus. In order to understand the coupling of external probes to the capsid, vibrational modes with atomic detail are essential. The standard approach to find the atomic modes of a molecule with $N$ atoms requires the formation and diagonlization of a $3N\times 3N$ matrix. As viruses have $10^5$ or more atoms, the standard approach is difficult. Using ideas from electronic structure theory, we have developed a method to construct the mechanical modes of large molecules such as viruses with atomic detail. Application to viruses such as the cowpea chlorotic mottle virus, satellite tobacco necrosis virus, and M13 bacteriophage show a fairly complicated picture of the mechanical modes. [Preview Abstract] |
Friday, March 14, 2008 8:48AM - 9:00AM |
X40.00005: Diversity of in-vivo assembled HIV-1 capsids Se Il Lee, Toan Nguyen Understanding the capsid assembly process of Human Immunodeficiency Virus (HIV), the causative agent of Acute Immuno Deficiency Syndrom (AIDS), is very important because of recent intense interest in capsid-oriented viral therapy. The unique conical shapes of mature HIV-1 capsid have drawn significant interests in the biological community and started to attract attention from the physics community. Previous studies showed that in a free assembly process, the HIV-1 conical shape is not thermodynamically stable. However, if the volume of the capsid is constrained during assembly and the capsid protein shell has high spontaneous curvature, the conical shape is stable. In this work, we focus on in-vivo HIV-1 capsid assembly. For this case, the viral envelope membrane present during assembly imposes constraint on the length of the capsid. We use an elastic continuum shell theory to approximate the energies of various HIV-1 capsid shapes (spherical, cylindrical and conical). We show that for certain range of viral membrane diameter, the conical and cylindrical shapes are both thermodynamically stable. This result is supported by experimental observation that in-vivo assembled HIV-1 capsids are very heterogeneous in shapes and sizes. Numerical calculation is also performed to improve theoretical approximation. [Preview Abstract] |
Friday, March 14, 2008 9:00AM - 9:12AM |
X40.00006: An elastic model of partial budding of retroviruses Rui Zhang, Toan Nguyen Retroviruses are characterized by their unique infection strategy of reverse transcription, in which the genetic information flows from RNA back to DNA. The most well known representative is the human immunodeficiency virus (HIV). Unlike budding of traditional enveloped viruses, retrovirus budding happens together with the formation of spherical virus capsids at the cell membrane. Led by this unique budding mechanism, we proposed an elastic model of retrovirus budding in this work. We found that if the lipid molecules of the membrane are supplied fast enough from the cell interior, the budding always proceeds to completion. In the opposite limit, there is an optimal size of partially budded virions. The zenith angle of these partially spherical capsids, $\alpha$, is given by $\alpha\simeq(\tau^2/\kappa\sigma)^{1/4}$, where $\kappa$ is the bending modulus of the membrane, $\sigma$ is the surface tension of the membrane, and $\tau$ characterizes the strength of capsid protein interaction. If $\tau$ is large enough such that $\alpha\sim\pi$, the budding is complete. Our model explained many features of retrovirus partial budding observed in experiments. [Preview Abstract] |
Friday, March 14, 2008 9:12AM - 9:24AM |
X40.00007: Calibrating elastic parameters from molecular dynamics simulations of capsid proteins Stephen Hicks, Christopher Henley Virus capsids are modeled with elastic network models in which a handful of parameters determine transitions in assembly [1] and morphology [2]. We introduce an approach to compute these parameters from the microscopic structure of the proteins involved. We consider each protein as one or a few rigid bodies with very general interactions, which we parameterize by fitting the simulated equilibrium fluctuations (relative translations and rotations) of a pair of proteins (or fragments) to a 6-dimensional Gaussian. We can then compose these generalized springs into the global capsid structure to determine the continuum elastic parameters. We demonstrate our approach on HIV capsid protein and compare our results with the observed lattice structure (from cryo-EM [3] and AFM indentation studies).\\{} [1] R. Zandi et al, PNAS 101 (2004) 15556.\\{} [2] J. Lidmar, L. Mirny, and D. R. Nelson, PRE 68 (2003) 051910.\\{} [3] B. K. Ganser-Pornillos et al, Cell 131 (2007) 70. [Preview Abstract] |
Friday, March 14, 2008 9:24AM - 9:36AM |
X40.00008: Coarse-grained mechanics of viral shells William S. Klug, Melissa M. Gibbons We present an approach for creating three-dimensional finite element models of viral capsids from atomic-level structural data (X-ray or cryo-EM). The models capture heterogeneous geometric features and are used in conjunction with three-dimensional nonlinear continuum elasticity to simulate nanoindentation experiments as performed using atomic force microscopy. The method is extremely flexible; able to capture varying levels of detail in the three-dimensional structure. Nanoindentation simulations are presented for several viruses: Hepatitis B, CCMV, HK97, and $\phi$29. In addition to purely continuum elastic models a multiscale technique is developed that combines finite-element kinematics with MD energetics such that large-scale deformations are facilitated by a reduction in degrees of freedom. Simulations of these capsid deformation experiments provide a testing ground for the techniques, as well as insight into the strength-determining mechanisms of capsid deformation. These methods can be extended as a framework for modeling other proteins and macromolecular structures in cell biology. [Preview Abstract] |
Friday, March 14, 2008 9:36AM - 9:48AM |
X40.00009: ABSTRACT HAS BEEN MOVED TO SESSION C1 |
Friday, March 14, 2008 9:48AM - 10:00AM |
X40.00010: Biochemistry in the Nanopores Samir M. Iqbal, Bala Murali Venkatesan, Demir Akin, Rashid Bashir Solid-state technology is fast advancing novel nano-structures for biomolecular detection. The solid-state nanopores have emerged as potential replacement of the Sanger's method for DNA sequencing. While the passage of the DNA molecule through the nanopore has been reported extensively, little has been done to identify the individual base pairs or sequences within the molecule. Learning from the mechanics of ion-channels on the cell surface, we functionalized the solid-state nanopores to recognize and selectively regulate the flow of molecules though the pore. The probe DNA was immobilized by chemical adsorption, and target DNA was passed under electrophoretic bias. The single base mismatch selectivity was achieved by using a hairpin loop in the probe. We could thus identify between the perfect complementary and mismatched target molecules. We will expand on the theoretical framework that governs the interactions of the probe and target molecules, as observed from the pulse behavior. [Preview Abstract] |
Friday, March 14, 2008 10:00AM - 10:12AM |
X40.00011: Poisson pulsed control of particle escape Marie McCrary, Lora Billings, Ira Schwartz, Mark Dykman We consider the problem of escape in a double well potential. With a weak background Gaussian noise, the escape rate is well known and follows an exponential scaling with the noise intensity $D$. Here, we consider adding a small Poisson noise to the Gaussian noise. We compute the change in escape time as we add Poisson distributed pulses of a given duration and amplitude. The escape rate acquires an extra factor which is determined by the characteristic functional of the Poisson noise calculated for a function, which is determined by the system dynamics and is inversely proportional to $D$. As a result, for small $D$ even weak Poisson pulses can lead to a significant change of the escape rate. The Poisson noise induced factor depends sensitively on the interrelation between the noise correlation time and the relaxation time of the system. We compare analytical results with extensive numerical simulations. The numerical computation of escape rates for multiple interacting particles in a well will also be shown. [Preview Abstract] |
Friday, March 14, 2008 10:12AM - 10:24AM |
X40.00012: Quorum sensing and biofilm formation investigated using laser-trapped bacterial arrays Vernita Gordon, John Butler, Ivan Smalyukh, Matthew Parsek, Gerard Wong Studies of individual, free-swimming (planktonic) bacteria have yielded much information about their genetic and phenotypic characteristics and about ``quorum sensing,'' the autoinducing process by which bacteria detect high concentrations of other bacteria. However, in most environments the majority of bacteria are not in the planktonic form but are rather in biofilms, which are highly-structured, dynamic communities of multiple bacteria that adhere to a surface and to each other using an extracellular polysaccharide matrix. Bacteria in biofilms are phenotypically very different from their genetically-identical planktonic counterparts.~ Among other characteristics, they are much more antibiotic-resistant and virulent.~ Such biofilms form persistent infections on medical implants and in the lungs of cystic fibrosis patients, where Pseudomonas aeruginosa biofilms are the leading cause of lung damage and, ultimately, death.~ To understand the importance of different extracellular materials, motility mechanisms, and quorum sensing for biofilm formation and stability, we use single-gene knockout mutants and an infrared laser trap to create a bacterial aggregate that serves as a model biofilm and allows us to measure the importance of these factors as a function of trapping time, surface, and nutritional environment. [Preview Abstract] |
Friday, March 14, 2008 10:24AM - 10:36AM |
X40.00013: Self-Polarization of Cells in Elastic Gels Assaf Zemel, Samuel Safran The shape of a cell as well as the rigidity and geometry of its surroundings play an important role in vital cellular processes. The contractile activity of cells provides a generic means by which cells may sense and respond to mechanical features. The matrix stresses, that depend on the elasticity and geometry of cells, feedback on the cells and influence their activity. This suggests a mechanical mechanism by which cells control their shape and forces. We present a quantitative, mechanical model that predicts that cells in an elastic medium can self-polarize to form well ordered stress fibers. We focus on both single cells in a gel, as well as on an ensemble of cells that is confined to some region within the gel. While the \textit{magnitude} of the cellular forces is found to increase monotonically with the matrix rigidity the \textit{anisotropy} of the forces, and thus the ability of the cells to polarize, is predicted to depend non-monotonically on the medium's rigidity. We discuss these results with experimental findings and with the observation of an optimal medium elasticity for cell function and differentiation. [Preview Abstract] |
Friday, March 14, 2008 10:36AM - 10:48AM |
X40.00014: Active suspensions in shear flow A. Ahmadi, M.C. Marchetti, T.B. Liverpool We report on the structure and rheology of an active suspension of cytoskeletal filaments and motor proteins in shear flow. Hydrodynamics equations for an active suspension were derived earlier by us [arXiv:q-bio.CB/0703029v1] by coarse-graining the Smoluchowski equation for a model of filaments and motors. The model incorporates the coupling of orientational order to flow and accounts for the exchange of momentum between filaments and solvent. In the present study we investigate the role of active crosslinkers on the formation and stability of ordered states (polar and nematic) under external shear flow. We also study the effect of motor activity on the rheological behavior of the ordered states away from boundaries. This work may also be relevant for the understanding of the flow-driven reorientation of endothelial cells under the shear stress imposed by blood flow. [Preview Abstract] |
Friday, March 14, 2008 10:48AM - 11:00AM |
X40.00015: Selective advantage for sexual replication with random haploid fusion Emmanuel Tannenbaum This talk develops a simplified set of models describing asexual and sexual replication in unicellular diploid organisms. The models assume organisms whose genomes consist of two chromosomes, where each chromosome is assumed to be functional if and only if it is equal to some master sequence. The fitness of an organism is determined by the number of functional chromosomes in its genome. For a population replicating asexually, a cell replicates both of its chromosomes, and then divides and splits its genetic material evenly between the two cells. For a population replicating sexually, a given cell first divides into two haploids, which enter a haploid pool. Within the haploid pool, haploids fuse into diploids, which then divide via the normal mitotic process. When the cost for sex is small, as measured by the ratio of the characteristic haploid fusion time to the characteristic growth time, we find that sexual replication with random haploid fusion leads to a greater mean fitness for the population than a purely asexual strategy. The results of this talk are consistent with previous studies suggesting that sex is favored at intermediate mutation rates, for slowly replicating organisms, and at high population densities. [Preview Abstract] |
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