This award supports theoretical and computational research at the interface of condensed matter physics and biology. The PI aims to study the physics of large viral assembly "intermediates" using fundamental methods of condensed matter physics. Current descriptions of the assembly of a viral capsid in a solution of capsid proteins, or oligomers, encounter a free energy barrier that is more than two orders of magnitude larger than the thermal energy. This barrier would forbid spontaneous viral assembly under conditions of thermal equilibrium, which conflicts with established in-vitro assembly studies. The PI will address this problem by applying methods borrowed from continuum physics, specifically the theory of elasticity of thin shells, which already has been found to be useful for the study of the shape and elastic response of viral shells. Analytical studies will be complemented by large-scale numerical studies combining finite-element analysis of the physics of viral shells with Monte-Carlo simulation in order to simulate the growth of a large viral shell and to compute the free-energy barrier against assembly. A second aim of the proposal is to study the effects of cooperativity on viral assembly. Frank Caspar proposed, already in 1980, that viral assembly is akin to other forms of protein aggregation, such as the polymerization of actin filaments, where the internal conformational degrees of freedom of the proteins are known to play a key self-regulatory role during aggregation. The PIs have determined how this concept can be quantitatively implemented in a study of viral assembly and how the effect of internal degrees of freedom on the assembly free energy barrier can be explored. They will compute, both analytically and numerically, the force-deformation curve of completed shells with internal degrees of freedom and test the results via AFM studies of CCMV, as part of an ongoing collaboration. The intellectual merit of the proposal lies in the application of important and powerful methods of solid-state physics, such as Kosterlitz-Thouless melting, surface melting, Wulff Construction, Soft-mode instability, and Grinfeld Instability to the physical studies of viruses. A broader impact of the proposed work would be the development of physical insight into the conditions that allow controlled self-assembly of large, ordered nanoshells with interesting potential materials science applications.
NON-TECHNICAL SUMMARY: This award supports theoretical and computational research at the interface of condensed matter physics and biology. The PI plans to apply concepts of fundamental condensed matter physics to understand biologically inspired problem of how proteins assemble themselves into the nanoscale-sized shells of viruses. The PIs will explore the relationship of this process to other self-assembly processes involving proteins. The work may have impact on understanding other processes where nanoscale-sized building blocks of atoms or molecules spontaneously arrange themselves into interesting structures, some with potential applications in medicine or technology more generally.
