A Multiscale Approach to Understanding and Designing Assembly Mechanisms

The organization of basic units into well-defined structures with exquisitely controlled dynamics is fundamental to biological systems and biomaterials. For example, viral proteins assemble into functional capsids with astonishing fidelity, while actin and microtubule networks dynamically coordinate to engineer cell motility. These processes are driven and directed by specific interactions between individual molecules, which are characterized by length and time scales that are many orders of magnitude smaller than those associated with a virus or a cell. Does specificity originate by creating larger structures, or does specificity at smaller scales create the larger scale structures?

Large-scale correlations in biology require collective interactions that are regulated by a tightly balanced competition of forces between individual molecules. It is difficult, with experiments alone, to parse these interactions for those factors that critically influence large scale properties. Thus, it is vital to complement experiments with theoretical and computational models, in which the effects of different interactions can be isolated and monitored, much like the effects of individual proteins can be determined by experiments with transgenic animals. The output of these models can drive and focus the formulation of new experiments. Advances in imaging methods that visualize collective interactions and single molecule techniques that probe specific species provide the perfect opportunity for synergy between theory and experiments.

In completed work, I integrated molecular dynamics simulations with coarse grain field-theoretic methods to study phenomena ranging from binding and unbinding of individual DNA base-pairs to meso-scale forces and dynamics generated by collective binding events. In my poster, I will outline how I plan to build on this experience to understand mechanisms of viral capsid assembly and to design new mechanisms to control the dynamics of synthetic assembly processes.