Physics of Viral Structure and Assembly

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The Division of Materials Research and the Division of Molecular and Cellular Biology jointly funds this award. This award supports theoretical condensed matter physics at the interface with biology. The PI seeks to develop a comprehensive statistical mechanical framework to describe the physical properties of viruses and of viral self-assembly. New experiments are raising basic questions relating to structural stability, symmetry, and pressure generation of viruses. The PI aims to address these questions with two objectives. The first objective is to provide a physical basis for viral structure and symmetry, which is currently justified in terms of the principles of quasi-equivalence and of genetic parsimony. Self-assembly experiments suggest that these concepts must be based on free energy minimization. The PI will employ a combination of methods with an aim to develop a meaningful free energy. The PI will utilize a statistical mechanical model for viral self-assembly that has been shown to reproduce both the main series of icosahedral capsids, exceptional non-icosahedral capsids and also cylindrical capsids. Numerical simulations of this model will be carried out to determine the full structure spectrum. Using these results together with modern statistical mechanical methods of self-assembling systems the PI will determine a general phase diagram for the assembly of both sphere-like and rod-like viruses. The work will be complemented by the use of Landau Theory to analyze the competition between icosahedral symmetry and non-icosahedral structures. The second objective is to develop a physical description of RNA encapsidation. A mechanical description of DNA encapsidation of phage viruses, which is powered by a molecular motor, is already available but the self-assembly of single-stranded RNA viruses is quite mysterious: viral RNA is spontaneously compressed during assembly without any external work being done. Self-assembly of linear polymers will be examined by classical analytical methods borrowed from polymer physics. In order to account for the secondary and tertiary RNA structure, we will apply the Isambert and Siggia description of RNA as a thermally fluctuating gel. Continuum elasticity theory will be used to model the encapsidation process and obtain the conditions for spontaneous assembly. The Isamber-Siggia statistical mechanical analysis will be used to demonstrate that the gel has negative Poisson Ratio, as apparently required by the continuum description. The research aims to extend modern methods of soft condensed matter theory, in areas such as self-assembly, polymer physics, entropic elasticity to emerging problems in the physics of viruses. While the synthesis of artificial protein cages is a rapidly developing area of materials science, the design criteria for self-assembled shells that can reproduce the remarkable properties of viral capsids are only beginning to be understood. Just as the theory of self-assembly now is used on a routine basis for the self-assembly of nanocages and quantum dots, a basic understanding of the physics of viral self-assembly should be a useful guide for the design of synthetic protein cages. A broader impact of this work is that it contributes to this basic understanding. It also provides graduate and postgraduate level educational experiences for the next generation of condensed matter theorists.%%%The Division of Materials Research and the Division of Molecular and Cellular Biology jointly funds this award. This award supports theoretical condensed matter physics at the interface with biology. The PI seeks to develop a comprehensive statistical mechanical framework to describe the physical properties of viruses and of viral self-assembly. Viruses lend themselves to the application of physics to microbiology. This is in part because of the extreme austerity of viral structure as compared with living organisms and because they do not carry out any autonomous metabolic processes. The combination of micro-mechanical manipulation methods and modern microscopy with molecular biology is now producing a new generation of physical studies of viruses. These experiments are raising basic questions relating to structural stability, symmetry, and pressure generation of viruses that the PI will address. The research aims to extend modern methods of soft condensed matter theory, in areas such as self-assembly, polymer physics, entropic elasticity to emerging problems in the physics of viruses. While the synthesis of artificial protein cages is a rapidly developing area of materials science, the design criteria for self-assembled shells that can reproduce the remarkable properties of viral capsids are only beginning to be understood. Just as the theory of self-assembly now is used on a routine basis for the self-assembly of nanocages and quantum dots, a basic understanding of the physics of viral self-assembly should be a useful guide for the design of synthetic protein cages. A broader impact of this work is that it contributes to this basic understanding. It also provides graduate and postgraduate level educational experiences for the next generation of condensed matter theorists.***