(432b) Theoretical Modeling of the Dynamics of Clathrin Self-Assembly Into Nanoscale Assemblies

Clathrin is a cytoplasmic protein that plays a critical role in endocytosis by forming the basket-like cages on the cell membrane that seed the formation of the endosome pits that transport cargo into the cell. A single clathrin complex adopts a pinwheel configuration. The aggregation of many clathrin pinwheels on a membrane or interface leads to lattice-like assemblies with a mixture of 5-, 6-, and 7-member rings. In vitro assembly of clathrin within a solution results in closed, nanoscale assemblies with various shapes and sizes. Our goal in this research is to develop a fundamental theoretical model for the thermodynamics and kinetics of clathrin assembly in 2 and 3 dimensions in order to guide experiments toward the assembly of targeted nanoscale assemblies. Towards this goal, we have developed a theoretical model for clathrin assembly that can address the assembly dynamics in 2 and 3 dimensions. The clathrin are modeled as effective pinwheels that form leg-leg associations and resist elastic bending deformation; thus, the pinwheels are capable of forming the range of ring structures that are observed experimentally. Our theoretical model combines Brownian dynamics simulations with dynamic mean field theory in order to track the motion of hundreds of clathrin pinwheels at sufficiently long time scales to achieve complete assembly. With this theoretical model, we predict the phase diagram for clathrin assembly and perform dynamic simulations for a range of quenches into the phase diagram. The resulting dynamics exhibit the hallmark behavior of spinodal decomposition with subsequent coarsening of ordered domains. The defect structures in the final configurations result in large-scale elastic stresses in the lattice network. We will then proceed to discuss the assembly of specific nanoscale assemblies for application in advanced materials applications.