Dr. Margaret E. Johnson

Modeling membrane reshaping driven by protein self-assembly


Self-assembly of protein components from solution to the plasma membrane is necessary for a variety of membrane remodelling processes such as clathrin-mediated endocytosis. Beyond assembly, the clathrin protein coat must bend the membrane, ‘package’ cargo, or otherwise not form a vesicle. In principle, these demands should all be simultaneously met in specific and overlapping regimes of concentration, energetics, and external activity, but at least in vitro, this is not the case. In recent work using theory and reaction-diffusion modelling validated by experimental kinetics, we quantified how the in vivo concentration of clathrin is too low to nucleate lattices in solution but will nucleate on membranes with sufficient adaptor proteins. Using a continuum mechanical model of membranes, we have further shown how the cost of bending the membrane scales with the size of the membrane lattice and its shape, providing strong selection for compact lattice growth when coupled to membrane bending. With our models, we assess how the net energetic cost of coupled assembly and membrane bending is influenced by protein scaffolding and proteins that induce curvature through helix insertion. Our models predict timescales of assembly and energetic dependence on membrane mechanics that can be tested experimentally, with the aim of determining necessary conditions for productive and cargo-laden vesicle formation.