Event Date and Time
Margaret E Johnson, Johns Hopkins University
Assembly of cytosolic proteins on membranes is essential for controlling transport and communication in and out of cells. The ability of these protein components to nucleate and assemble on membranes can be triggered through both ATP-independent processes, and through energy-consuming reactions such as phosphorylation. We recently constructed a simple theoretical model to quantify how dimensional reduction from 3D to 2D can, on its own, provide a powerful driving force promoting assembly after membrane localization, thereby regulating the timing of assembly. Clathrin-mediated endocytosis, an essential process for internalizing transmembrane cargo across the cell membrane, provides a rich system for studying how assembly is controlled via stochastic and active forces. Using kinetic modeling and new reaction-diffusion algorithms developed by our lab, we show how the stoichiometry of the assembly components, which can be effectively controlled via enzymatic reactions (which turn on and off interactions), can control the kinetics and success of clathrin assembly. We quantify how specific assembly components can stabilize assembly growth through the formation of 2D interactions on the surface and through cooperativity driven by specific protein-protein interactions. Recently, we have used continuum thin-film models to characterize how specific classes of proteins can create mechanical feedback that renders the membrane effectively more ‘sticky’ to subsequent protein recruitment interactions. With experimental measurements on protein localization to membranes, we are using theory and simulation to build predictive models of active protein assembly in vivo.