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Center for Nonlinear Studies |
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, can control the kinetics and success of clathrin assembly. We show that specific assembly components stabilize assembly nucleation and growth through 2D localization along with cooperativity, in quantitative agreement with in vitro fluorescence data. 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. Our NERDSS reaction-diffusion software enables a broad range of simulations of mesoscale self-assembly and self-organization over long time-scales comparable with experiment. We are combining theory and simulation to predict how assembly of diverse multi-protein complexes can be controlled in the nonequilibrium environment of the cell.
Host: Sumantra Sarkar and Angel Garcia