Modeling membrane reshaping driven by dynamic protein assemblies

Abstract

Remodeling of membranes in living systems is almost universally coupled to self-assembly of soluble proteins. Proteins assemble into semi-rigid shells that reshape attached membranes, and into filaments that protrude membranes. These assemblies are temporary, building from reversible protein and membrane interactions that must nucleate in the proper location. The interactions are strongly influenced by the nonequilibrium environment of the cell, such as gradients of components or active modifications by kinases. From a modeling perspective, understanding mechanisms and control thus requires 1. time-dependent approaches that ideally incorporate 2. macromolecular structure, 3. out-of-equilibrium processes, and 4. deformable membranes over microns and seconds. Realistically, tradeoffs must be made with these last three features. However, we see recent developments from the highly coarsened molecule-based scale, the continuum reaction-diffusion scale, and hybrid approaches as stimulating efforts in diverse applications. We discuss here methodological advances and progress towards simulating these processes as they occur physiologically.