Bulletin of the American Physical Society
APS March Meeting 2020
Volume 65, Number 1
Monday–Friday, March 2–6, 2020; Denver, Colorado
Session D30: Self-Limiting Assemblies I: Functional Structures in BiologyFocus
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Sponsoring Units: DSOFT DPOLY DBIO Chair: Michael Hagan, Brandeis Univ Room: 502 |
Monday, March 2, 2020 2:30PM - 2:42PM |
D30.00001: How do cells control the length of their flagella? Prathitha Kar, Thomas Fai, Lishibanya Mohapatra, Jane Kondev, Ariel Amir Cells assemble a number of filamentous structures which have a specific length. The question of how cells control the length has been studied extensively in model organism Chlamydomonas reinhardtii which has two flagella of the same length. |
Monday, March 2, 2020 2:42PM - 2:54PM |
D30.00002: Size regulation of multiple intracellular structures self-assembled from a shared resource pool Deb Banerjee, Shiladitya Banerjee How cells regulate the size of filamentous structures, networks and organelles, despite continuous turnover in their component parts, is a longstanding question. Recent experiments suggest that size control of many intracellular structures and organelles is achieved through depletion of a limiting subunit pool in the cytoplasm. While the limiting pool mechanism ensures organelle size scaling with cell size, it does not provide a mechanism for sensing and regulating individual organelle size. |
Monday, March 2, 2020 2:54PM - 3:06PM |
D30.00003: Energy cost of protein gradient formation in cells Arnab Datta Cells make protein gradients for various purposes, such as establishing position information in development or defining cell polarity in the process of cell division. Two classes of mechanisms for maintaining protein gradients in cells have been reported in the literature: i. those that combine protein diffusion and degradation, and ii. mechanisms that involve active transport of proteins by molecular motors. An example of the first mechanism is the Bicoid protein gradient in the Drosophila embryo, which provides positional information to the nuclei during development. A Smy1 gradient along actin cables in budding yeast cells regulates cable length and is formed by active transport of the proteins by myosin motors to the bud neck [1]. Establishing and maintaining these protein gradients require cells to expend energy. In this talk I examine different mechanisms of gradient formation in cells and estimate the energy costs associated with them. I also consider the scaling of the energy expenditure with cell size for the two different models of gradient formation, and discuss when one mechanism is energetically less costly than the other. |
Monday, March 2, 2020 3:06PM - 3:18PM |
D30.00004: First passage times in multi-protein self-assembly BHAVYA MISHRA, Margaret Johnson Self-assembly of proteins is essential for various cellular processes such as signalling, and clathrin-mediated endocytosis. In general, proteins diffuse in a 3D solution and recruit other proteins. But they can also localize to a 2D membrane surface via lipids. In a recent study, we quantified how localization of proteins to a 2D surface from 3D solution reduces their search space and proteins can exploit this dimensionality reduction to trigger self-assembly. Here we show how localization can in many cases accelerate the assembly process, despite significantly slower diffusion on the 2D surface. We formulate the self-assembly of protein binding pairs as first-passage problems and calculate the mean time to approach the thermodynamic equilibrium. We can theoretically approximate the role of localization in slowing or accelerating the overall assembly process and the regimes where diffusion becomes a limiting factor. We validate these predictions against numerical solutions using reaction-diffusion simulations. These results highlight the role of diffusion versus binding rates and concentration in controlling time-scales of assembly. |
Monday, March 2, 2020 3:18PM - 3:30PM |
D30.00005: Quantifying kinetics of multi-protein self-assembly, remodeling, and disassembly YIBEN FU, Margaret Johnson In the cell, multi-protein assemblies cannot persist forever and must ultimately disassemble through active or spontaneous processes. Protein assemblies involved in virion formation and clathrin-coat formation also appear to undergo dynamic remodelling which is critical for successful function. We show here using reaction-diffusion simulations how the kinetics of these assembly and disassembly processes can be sensitively tuned by the binding kinetics and cooperative interactions of the coat components and the molecules linking them to the membrane. We determine regimes where assembled structures can spontaneously remodel or disassemble. For stable structures, we then predict how enzymatic reactions can be exploited to locally destabilize links to the membrane and drive remodelling and disassembly. Using our recently developed NERDSS software, these models generate space and time-dependent predictions that can be compared directly with experiment. Our generalized computational methods can directly simulate a broad range of assembly processes at the cell-scale, providing a natural companion to quantitative cell biology. |
Monday, March 2, 2020 3:30PM - 4:06PM |
D30.00006: Theoretical principles of viral shell assembly and self-organization Invited Speaker: Roya Zandi Spherical crystals are elementary models of geometric frustration in materials, with important realizations in a range of systems from viral shells and fullerenes to particle- and molecular-coated droplets. Using continuum elasticity theory, we study the structure and elastic energy of ground states of crystalline caps conforming to a spherical surface. We find that the ground states consist of positive disclination defects and that the ground states with icosahedral subgroup symmetries in caps arise across a range of curvatures, even far from the closure point of complete shells. Further, we use Monte Carlo simulations to investigate the kinetic pathway of formation of viral shells (capsids) and find that the key for the formation of perfect icosahedral capsids is in the strength of elastic energy compared to the protein-protein interactions and the chemical potential of free subunits. |
Monday, March 2, 2020 4:06PM - 4:18PM |
D30.00007: Computational modeling to explain Hepatitis-B Virus capsid assembly, dimorphism, and disruption by antiviral drugs Farzaneh Mohajerani, Botond Tyukodi, Christopher Schlicksup, Jodi Hadden, Adam Zlotnick, Michael Hagan Assembly of the outer protein shell (capsid) of a virus is an essential step in its lifecycle. Understanding the mechanisms underlying assembly and the factors that determine the final morphology will guide development of antiviral drugs that disrupt or redirect assembly processes. Hepatitis-B Virus (HBV) assembles from a single capsid protein, which adopts different conformations to form icosahedral capsids with different sizes containing 180 or 240 proteins, T=3 or T=4 respectively in the Caspar-Klug nomenclature. Despite intensive experimental and theoretical investigation, the assembly pathways and mechanisms that control HBV dimorphism remain unclear. |
Monday, March 2, 2020 4:18PM - 4:30PM |
D30.00008: Thermodynamic and kinetic aspects of polymorphism in core controlled assembly of virus-like particles Alireza Ramezani, Orfeas Agis Karachalios, Paul Van der Schoot, Roya Zandi Motivated by recent experiments we investigate the phenomenon of polymorphism in core- controlled self-assembly of virus-like particles, where identical nanoparticles are encapsulated in capsids with different sizes. Our goal is to understand how protein concentration, stoichiometry and preferred curvature of capsids influence the prevalence of one shell size over another one. Using the equilibrium statistical physics and classical nucleation theory, we study how kinetic traps modify the state diagrams. We find that the free energy penalty associated with the rim proteins that have fewer favorable contacts with other proteins plays an important role in determining the capsid size. We show that in and out of equilibrium phase diagrams differ significantly and that kinetics favors the co-existence of capsids with different sizes at large stoichiometric ratios and/or protein concentration. |
Monday, March 2, 2020 4:30PM - 4:42PM |
D30.00009: RNA-mediated capsid nucleation of bacteriophage MS2 coat proteins confers RNA packaging selectivity Timothy Chiang, Rees F Garmann, Aaron Goldfain, LaNell A. Williams, Vinothan Manoharan Simple viruses, such as bacteriophage MS2, spontaneously assemble into a protein shell encapsulating a single molecule of genomic RNA. Infection of host cells by MS2 results in replication of the RNA and expression of viral coat proteins, which then package the cognate viral RNA with high selectivity despite the presence of competing host RNAs. How the MS2 coat proteins selectively self-assemble around their own RNA is poorly understood. Using interferometric scattering microscopy and quantitative gel electrophoresis, we show that the RNA-mediated nucleation-and-growth assembly pathway of MS2 coat proteins can drive preferential encapsidation of cognate RNA, and hence selective packaging. |
Monday, March 2, 2020 4:42PM - 4:54PM |
D30.00010: Role of C-Terminal "Arms" in the Assembly and Stability of SV40 Polymorphs Curt Waltmann, Monica Olvera De La Cruz, Roi Asor, Uri Raviv We study SV40 polymorphs by simulating the templated assembly process of VP1 pentamers. The simulations incorporate electrostatic effects and the connections formed between VP1 proteins by C-terminal flexible lateral units, termed here "arms". During assembly, VP1 pentamers connect to partial capsids before they bind to the template. The strength of these connections along with salt concentration can be manipulated leading to incomplete particles, T=1 particles, or aggregates of VP1 pentamers. In contrast to all other configurations, which are dynamic, the T=1 particles are static. The ability of VP1 pentamers to connect to other VP1 pentamers combined with the dynamic rearrangement of particles other than T=1 allows capsids to continue growing even when they are "pseudo-closed". The assembly mechanism described here is likely applicable to T=7 capsids. |
Monday, March 2, 2020 4:54PM - 5:06PM |
D30.00011: Linking Capsomere Elasticity with Virus Capsid Size and Patterning Lauren Nilsson, JCS Kadupitiya, Vikram Jadhao Self-limiting spontaneous assembly of proteins gives rise to many structures, including virus capsids. Often copies of a single type of protein are capable of assembling into an empty shell. Higher T-number viruses of this type, such as Hepatitis B virus (HBV), present an interesting challenge to model. Though these capsids exhibit a ubiquitous icosahedral symmetry, they can display distinct tiling patterns resulting from individual capsomeres in quasi-equivalent states. In order to model the assembly of these capsids, rigid-body models either use multiple monomeric subunits with different geometries or pre-formed pentamers and hexamers with fine-tuned interactions. We introduce SOUFFLE, a molecular dynamics simulation method with elastic capsomeres, to investigate capsid assembly. The method is used to study a model T1 system as well as nucleating tiling patterns associated with T3 and T4 HBV capsids. The assembly of full T3 and T4 capsids using pentamers and hexamers pre-formed with elastic capsomeres is also probed. Based on tiling-patterns and assembly diagrams, we propose that the heterogeneity of HBV capsids can be attributed to relatively low bending modulus of its capsomeres (10-15 kB T). |
Monday, March 2, 2020 5:06PM - 5:18PM |
D30.00012: Bulk light-scattering measurements of viral capsid self-assembly around RNA. LaNell A. Williams, Timothy Chiang, Rees F Garmann, Vinothan Manoharan Self-assembly is a vital part of the RNA virus life cycle. The assembly of viral coat proteins around viral RNA occurs both in vivo and in vitro, suggesting that viral capsid assembly may be driven by minimization of free energy. To better understand this process, we modify the interactions between coat proteins and between the coat proteins and RNA of MS2 bacteriophage in vitro by varying the ionic strength and pH, and we study the assembly using dynamic and static light scattering. From dynamic light scattering we determine the assembly yield and the size distribution of assembled products. From static light scattering, we measure the kinetics of assembly in bulk. By comparing the results from these two different techniques to each other and to results from gel electrophoresis, we infer features of the assembly pathway. |
Monday, March 2, 2020 5:18PM - 5:30PM |
D30.00013: Membrane tubulation induced by chiral crescent-shaped proteins Hiroshi Noguchi In living cells, structures of biomembranes are regulated by various proteins. We studied the protein assembly and membrane remodeling using coarse-grained meshless membrane simulations. We revealed how chirality of crescent-shaped protein rods changes their assembly and tubulation. The achiral rods deformed the membrane tube into an elliptical shape by stabilizing the edges of the ellipse. In contrast, the chiral rods formed a helical assembly that generated a cylindrical membrane tube with a constant radius in addition to the elliptical tube. This helical assembly could be further stabilized by the direct side-to-side attraction between the protein rods. The chirality also promotes the tubulation from a flat membrane. These results agree with experimental findings of the constant radius of membrane tubules induced by Bin/Amphiphysin/Rvs (BAR) superfamily proteins. |
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