Protein-driven lipid domain nucleation in biological membranes

Abstract

Lipid rafts are heterogeneous dynamic lipid domains of the cell membranes that are involved in several biological processes, such as protein and lipid specific transport and signaling. Our understanding of lipid raft formation is still limited due to the transient and elusive nature of these domains in vivo, in contrast with the stable phase-separated domains observed in artificial membranes. Inspired by experimental findings highlighting the relevance of transmembrane proteins for lipid rafts, we investigate lipid domain nucleation by coarse-grained molecular dynamics and Ising-model simulations. We find that the presence of a transmembrane protein can trigger lipid domain nucleation in a flat membrane from an otherwise mixed lipid phase. Furthermore, we study the role of the lipid domain in the diffusion of the protein showing that its mobility is hindered by the presence of the raft. The results of our coarse-grained molecular-dynamics and Ising-model simulations thus coherently support the important role played by transmembrane proteins in lipid domain formation and stability.