Mechanisms Governing Protein Clustering and Shape Changes in Biological Membranes

Abstract

A characteristic feature of eukaryotic cells is the variety of membrane bound organelles, distinguished by their unique morphology and chemical composition. Despite the differences in membrane composition across organelles, ramified, tubular or sheet-like shapes are generic large scale morphologies observed in internal membranes, which suggest involvement of common underlying principles. While there is detailed knowledge of the molecular processes involved in membrane remodelling at short scales, our understanding of the underlying physical principles governing large scale morphogenesis is still rudimentary. One common aspect is that membranes are subject to the action of curvature sensing and curvature generating proteins which modulate local membrane shape and lipid composition. Even at relatively small values of surface coverage these proteins can cluster through to a variety or processes and trigger morphological changes which are important for singling. Another important feature, specific to organelle membranes, especially those in the trafficking pathways, is that they are subject to and driven by a continuous flux of membrane bound materials, on time scales comparable to membrane relaxation times. Here we present Monte Carlo Simulation models that tests the effect of the above processes on the morphology of the membranes. We find that the steady state shapes obtained as a result of such active processes, bear a striking resemblance to the ramified morphologies of organelles in vivo, pointing to the relevance of nonequilibrium fission-fusion in organelle morphogenesis. We show that, due to membrane curvature and composition interactions, the curvature-inducing membrane-nematogens can aggregate spontaneously, even at low concentrations, leading to a variety of membrane morphologies such as tubular and the sheet conformations. Strong lipid-protein interaction can result in fast protein clustering indicating a route to a lipid mediated signal amplification.