Domain Interfaces Facilitate Protein Association and Aggregation in Multicomponent Lipid Bilayers

Abstract

Model lipid bilayers that mimic the lateral heterogeneity observed in biological membranes are increasingly used to probe protein assembly, cellular signaling, vesicle fusion, and membrane protein activity. Consensus is yet to emerge on the driving forces of protein co-localization in domain separated membranes. Difficulty in locating domain boundaries and accurate predictions of their contribution to free energy presents further challenges. Employing coarse-grained molecular dynamics simulations of multicomponent lipid membranes with multiple copies of transmembrane proteins, we investigate protein migration and local membrane properties such as membrane curvature and thickness that drives these processes. We report that proteins predominantly migrate to the interface between ordered and disordered stripe domains and stabilizes the interface by reducing domain interface free energies by 40%-50% via a new interface detection algorithm.