Modeling nonequilibrium self-assembly in the cell through reaction-diffusion simulation

In diverse cellular pathways including clathrin-mediated endocytosis (CME) and viral bud formation, cytosolic proteins must self-assemble and induce membrane deformation. These essential processes require localization to the membrane at particular times within the cell, relying in part on the nonequilibrium activity of energy consuming kinases, phosphatases, and ATPases to produce robust and reversible assemblies. Current computational tools for studying self-assembly dynamics are not feasible for simulating cellular dynamics due to the slow time-scales and the dependence on energy-consuming events. We recently developed novel reaction-diffusion algorithms and software that enable detailed computer simulations of nonequilibrium self-assembly over long time-scales. Our simulations of clathrin-coat assembly in CME reveal how the formation of structured lattices impacts the kinetics of assembly, and how localization to the membrane can stabilize large, dynamic assemblies not observed in solution. We also recently developed a relatively simple theory to quantify how localization of protein binding partners to the membrane can dramatically enhance binding, via reduction of dimensionality. Membrane localization can thus provide a trigger for assembly.