Atomistic molecular dynamics simulations of concentrated protein solutions in the presence of a phospholipid bilayer are presented to gain insights into the dynamics and interactions at the cytosol-membrane interface. The main finding is that proteins that are not known to specifically interact with membranes are preferentially excluded from the membrane, leaving a depletion zone near the membrane surface. As a consequence, effective protein concentrations increase, leading to increased protein contacts and clustering, whereas protein diffusion becomes faster near the membrane for proteins that do occasionally enter the depletion zone. Since protein-membrane contacts are infrequent and short-lived in this study, the structure of the lipid bilayer remains largely unaffected by the crowded protein solution, but when proteins do contact lipid head groups, small but statistically significant local membrane curvature is induced, on average.
Keywords: crowding; diffusion; membrane curvature; molecular dynamics; phospholipids.