Modeling the mechanisms through which protein phase separation induces membrane curvature.

Abstract

Membrane curvature is an essential component of life. Many cellular processes, such as endocytosis, exocytosis, and cell motility induce curvature in membranes to carry out their functions. Though it is traditionally thought that structured proteins drive curvature, recent work has shown that disordered proteins can also be potent drivers of curvature. In particular, liquid-like condensation of disordered proteins has recently been shown to produce concave membrane curvature, resulting in protein-lined buds and tubules of the membrane. However, the mechanism behind this phenomenon remains poorly understood. Here we seek to understand the protein-protein and protein-membrane interactions that give rise to these behaviors. We begin by using coarse grained molecular dynamics simulations to investigate the conformational preferences of disordered proteins under different conditions: in varying salt concentrations, in solution or tethered to a lipid membrane. Specifically, we examine the deviation of disordered protein behavior from that of a simple random walk, both in solution and on membrane surfaces. By comparing modeling results to experimental data, we separate the role of protein-protein and protein-membrane interactions to shed light on the role of each in both phase separation and curvature generation. Our work will provide insight on the role that disordered regions have in membrane complexes, particularly those which facilitate membrane curvature.