Bulletin of the American Physical Society
APS March Meeting 2014
Volume 59, Number 1
Monday–Friday, March 3–7, 2014; Denver, Colorado
Session J16: Focus Session: Soft Matter Perspectives on Protein Self-Assembly II |
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Chair: Michael Hagan, Brandeis Room: 401 |
Tuesday, March 4, 2014 2:30PM - 2:42PM |
J16.00001: Arrest scenarios in concentrated protein solutions - from hard sphere glasses to arrested spinodal decomposition Anna Stradner, Saskia Bucciarelli, Lucia Casal, Giuseppe Foffi, George Thurston, Bela Farago, Peter Schurtenberger The occurrence of an arrest transition in concentrated colloid suspensions and its dependence on the interaction potential is a hot topic in soft matter. Such arrest transitions can also occur in concentrated protein solutions, as they exist e.g. in biological cells or are increasingly used in pharmaceutical formulations. Here we demonstrate the applicability of concepts from colloid science to understand the dynamics of concentrated protein solutions. In this presentation we report a combination of 3D light scattering, small-angle X-ray scattering and neutron spin echo measurements to study the structural properties as well as the collective and self diffusion of proteins in highly concentrated solutions on the relevant length and time scales. We demonstrate that various arrest scenarios indeed exist for different globular proteins. The proteins chosen are different bovine lens crystallins. We report examples of hard and attractive glass transitions and arrested spinodal decomposition directly linked to the effective pair potentials determined in static scattering experiments for the different proteins. We discuss these different arrest scenarios in view of possible applications of dense protein solutions as well as in view of their possible relevance for living systems. [Preview Abstract] |
Tuesday, March 4, 2014 2:42PM - 2:54PM |
J16.00002: The bacterial cytoplasm has glass-like properties and is fluidized by metabolic activity Brad Parry, Ivan Surovtsev, Matthew Cabeen, Corey O'Hern, Eric Dufresne, Christine Jacobs-Wagner In eukaryotes, active transport involves motor proteins and cytoskeletal filaments. In contrast, bacteria (which lack cytoskeletal motor proteins) are thought to rely on diffusion for molecular transport, though the physical properties of the bacterial cytoplasm are poorly understood. Through single particle tracking of foreign particles of different sizes, we have found that the bacterial cytoplasm exhibits striking similarities to glass-forming liquids. Glass-forming liquids are noted for their metastability near the glass transition where their behavior changes from liquid-like to amorphous solid with even small perturbations. Particles of different sizes exhibit distinct dynamics and their mobility changes from fluid-like to glassy with increasing size. This size dependency provides an explanation for previous reports of both normal and anomalous diffusion in the bacterial cytoplasm. Moreover, we find that cellular metabolism attenuates the glassy properties of the bacterial cytoplasm. As a result, components that would otherwise be caged in narrow regions of confinement are able to explore the cytoplasmic space under metabolically active conditions. These findings have broad implications for our understanding of bacterial physiology as the glassy behavior of the cytoplasm impacts all intracellular processes involving large cellular components. [Preview Abstract] |
Tuesday, March 4, 2014 2:54PM - 3:06PM |
J16.00003: Dynamic clusters in highly concentrated lysozyme solutions S.D. Hudson, P.D. Godfrin, L. Porcar, P. Falus, K. Hong, N.J. Wagner, Y. Liu New biologic drugs need to be highly concentrated to have the required dosage for injection. Such high concentrations pose challenges for solution viscosity and stability. We therefore have studied the viscosity and dynamic clustering behavior of concentrated (up to 500 mg/mL) lysozyme solutions. Cluster dynamics are measured by neutron spin echo scattering experiments, which yield the mutual diffusivity. Viscosity is measured with a miniature capillary viscometer. While static scattering indicates cluster-like organization, the dynamic measurements show that these are momentary and do not survive local diffusion times. At high concentrations, they persist and diffusivity and viscosity dramatically increase. [Preview Abstract] |
Tuesday, March 4, 2014 3:06PM - 3:42PM |
J16.00004: An overview of protein phase behavior Invited Speaker: Neer Asherie A homogenous protein solution can undergo several transformations when the conditions are changed. The proteins can form crystals, dense liquid phases, aggregates and gels. These transformations are central to numerous practical applications, such as protein x-ray crystallography, protein condensation diseases and the industrial purification of proteins. In this talk I review the efforts that have been made over the past twenty years to understand protein phase behavior from a physical perspective with an emphasis on globular proteins in aqueous solution. I also present recent insights and conclude with some ideas for future directions. [Preview Abstract] |
Tuesday, March 4, 2014 3:42PM - 3:54PM |
J16.00005: A residue level protein-protein interaction model in electrolyte solutions Xueyu Song The osmotic second virial coefficients $B_{2}$ are directly related to the solubility of protein molecules in electrolyte solutions and can be useful to narrow down the search parameter space of protein crystallization conditions. Using a residue level model of protein-protein interaction in electrolyte solutions $B_{2}$ of bovine pancreatic trypsin inhibitor and lysozyme in various solution conditions such as salt concentration, pH and temperature are calculated using an extended Fast Multipole Methods in combination with the boundary element formulation. Overall, the calculated $B_{2}$ are well correlated with the experimental observations for various solution conditions. In combination with our previous work on the binding affinity calculations of protein complexes it is demonstrated that our residue level model can be used as a reliable model to describe protein-protein interaction in solutions. [Preview Abstract] |
Tuesday, March 4, 2014 3:54PM - 4:06PM |
J16.00006: The role of crystal contacts in protein crystallization: soft matter characterization of two protein families Diana Fusco, Jeffrey Headd, Alfonso De Simone, Jun Wang, Patrick Charbonneau Crystallizing proteins is the bottleneck to systematically determining their structures, which are key to understanding certain biological processes and engineering bio-inspired materials. Identifying the conditions under which proteins crystallize should be equivalent to determining their phase diagram, but one typically resorts to combinatorial rather than physics-based sampling of solution conditions to tackle this difficult problem. Although several soft matter ``patchy particle'' models have been suggested to rationalize the phase behavior of proteins, the interactions that drive crystallization are insufficiently characterized for them to be of much use. We use atomistic simulations of solvated proteins of the rubredoxin family to parameterize patchy models. Their phase diagram is then compared with experimental crystallization conditions. The agreement between model and experiment supports the suitability of patchy models to describe globular proteins crystallization and provides physical guidelines to systematically improve protein crystallization experiments. An analogous analysis of ubiquitin, which crystallizes in multiple crystal forms, further clarifies the role of competing patches in controlling crystal assembly. [Preview Abstract] |
Tuesday, March 4, 2014 4:06PM - 4:18PM |
J16.00007: Getting Closer to Real Proteins: Asymmetric and Competing Interactions in Patchy Models Patrick Charbonneau, Diana Fusco Patchy particle models have been proposed to describe protein crystal assembly. Previous analyses of these models typically assume homogeneous patch interactions and symmetric patch geometry, but recent studies suggest otherwise. Typical protein interactions have a wide range of strengths, and sterically competing interactions are the rule rather than the exception. More complex patchy models are thus needed to guide protein crystallization. We study the phase diagram and assembly kinetics of patchy models with varying interaction strength and spatial distribution asymmetry. The results rationalize George and Wilson's observation that proteins with a second virial coefficient within a specific range are easier to crystallize and provide guidelines to facilitate crystallization of recalcitrant proteins. In models with sterically competing patches we also observe distinct crystal forms (dimeric vs. monomeric) depending on the relative strength of the secondary patches. [Preview Abstract] |
Tuesday, March 4, 2014 4:18PM - 4:30PM |
J16.00008: Design rules for the self-assembly of a protein crystal Stephen Whitelam, Thomas Haxton Theories and models of protein crystallization based on spheres that form close-packed crystals suggest that protein crystallization can be enhanced by metastable liquid-liquid criticality or demixing, and can be predicted by the osmotic second virial coefficient. However, most protein crystals are open structures, stabilized by anisotropic interactions. I will use analytic theory and computer simulations to argue that the self-assembly of open crystal lattices should not in general be best near the metastable liquid-liquid critical point or binodal (although assembly can certainly happen there), and to argue that the second virial coefficient cannot be a fully predictive measure of assembly propensity (although it is a useful starting point). Instead, the conditions that lead to best self-assembly of one particular computer model of a porous protein crystal are closer to the conditions that lead to best self-assembly of certain model viral capsids than they are to the conditions that optimize assembly of close-packed crystals.\\[4pt] References:\\[0pt] Haxton \& Whitelam Soft Matter 2012 \& 2013\\[0pt] Whitelam PRL 2010\\[0pt] Whitelam JCP 2010 [Preview Abstract] |
Tuesday, March 4, 2014 4:30PM - 4:42PM |
J16.00009: Shifting Phases for Patchy Particles -- Effect of mutagenesis and chemical modification on the phase diagram of human gamma D crystallin Jennifer J. McManus, Susan James, Ruth McNamara, Michelle Quinn Single mutations in human gamma D crystallin (HGD), a protein found in the eye lens are associated with several childhood cataracts. Phase diagrams for several of these protein mutants have been measured and reveal that phase boundaries are shifted compared with the native protein, leading to condensation of protein in a physiologically relevant regime. Using HGD as a model protein, we have constructed phase diagrams for double mutants of the protein, incorporating two single amino acid substitutions for which phase diagrams are already known. In doing so, the characteristics of each of the single mutations are maintained but both are now present in the same protein particle. While these proteins are not of interest physiologically, this strategy allows the controlled synthesis of nano-scale patchy particles in which features associated with a known phase behavior can be included. It can also provide a strategy for the controlled crystallisation of proteins. Phase boundaries also change after the chemical modification of the protein, through the covalent attachment of fluorescent labels, for example, and this will also be discussed. [Preview Abstract] |
Tuesday, March 4, 2014 4:42PM - 4:54PM |
J16.00010: Phase Transitions in Antibody Solutions: from Pharmaceuticals to Human Disease Ying Wang, Aleksey Lomakin, George Benedek Antibodies are very important proteins. Natural antibodies play essential role in the immune system of human body. Pharmaceutical antibodies are used as drugs. Antibodies are also indispensable tools in biomedical research and diagnostics. Recently, a number of observations of phase transitions of pharmaceutical antibodies have been reported. These phase transitions are undesirable from the perspective of colloid stability of drug solutions in processing and storage, but can be used for protein purification, X-ray crystallography, and improving pharmokinetics of drugs. Phase transitions of antibodies can also take place in human body, particularly in multiple myeloma patients who overproduce monoclonal antibodies. These antibodies, in some cases, crystallize at body temperature and cause severe complications called cryoglobulinemia. I will present the results of our current studies on phase transitions of both pharmaceutical antibodies and cryoglobulinemia-associated antibodies. These studies have shown that different antibodies have different propensity to undergo phase transitions, but their phase behavior has universal features which are remarkably different from those of spherical proteins. I will discuss how studies of phase behavior can be useful in assessing colloid stability of pharmaceutical antibodies and in early diagnostics of cryoglobulinemia, as well as general implications of the fact that some antibodies can precipitate at physiological conditions. [Preview Abstract] |
Tuesday, March 4, 2014 4:54PM - 5:06PM |
J16.00011: Structure of biological graded refractive index materials, and possible routes to self-assembly Jing Cai, Paul Heiney, Alison Sweeney For a camera-like eye, a spherical lens with a radially graded refractive index is required for high-quality image formation. Squids have evolved this lens design, and the index gradient results from variation in the density of protein in the lens from the center (70\% packing fraction) to the periphery (2\% packing fraction). However, density fluctuations must also remain low in all regions to maintain lens transparency. Squids have achieved this by an evolutionary radiation of the isoforms of one protein, S-crystallin; different protein isoforms are synthesized in different radial positions of the lens. We studied whether these proteins self-assemble into the observed gradient index material. X-ray scattering was performed on both intact lenses and solubilized lens protein. Our results show that protein packing is organized, and that the organization changes with radial position. We identify possible self-assembled routes to the observed structures via the predicted interactions between the proteins. Our study may provide insights into engineering new self-assembling graded refractive index materials. [Preview Abstract] |
Tuesday, March 4, 2014 5:06PM - 5:18PM |
J16.00012: ABSTRACT WITHDRAWN |
Tuesday, March 4, 2014 5:18PM - 5:30PM |
J16.00013: How Single-site Mutation Affects HP Lattice Proteins Guangjie Shi, David P Landau, Thomas Vogel, Thomas W\"{u}st, Ying Wai Li We developed a heuristic method based on Wang-Landau\footnote{T. W\"{u}st and D. P. Landau, J. Chem. Phys. \textbf{137}, 064903 (2012).} and multicanonical sampling for determining the ground-state degeneracy of HP lattice proteins \footnote{K. A. Dill, Biochemistry 24, 1501 (1985); K. F. Lau and K. A. Dill, Macromolecules 22, 3986 (1989). }. Our algorithm allowed the most precise estimations of the (sometimes substantial) ground-state degeneracies of some widely studied HP sequences. We investigated the effects of single-site mutation on specific long HP lattice proteins comprehensively, including structural changes in ground-states, changes of ground-state degeneracy and thermodynamic properties of the systems. Both extremely sensitive and insensitive cases have been observed; consequently, properties such as specific heat, tortuosities etc. may be either largely unaffected or may change significantly due to mutation. More interestingly, mutation can even induce a lower ground-state energy in a few cases. [Preview Abstract] |
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