Coarse-Grained Molecular Dynamics Simulations of an Inhomogeneous Ternary Lipid Bilayer

Abstract

Lateral, phase-separated microdomains form in model membranes composed of multi-component lipid mixtures. Similar structures are hypothesized to be of significant functional relevance in biological membranes. Though intensely studied, the molecular-level structures of these domains as yet remain unclear. We present coarse-grained molecular dynamics simulations (employing the MARTINI force-field) of a bilayer containing a ternary mixture of glycerophospholipids (saturated DPPC and unsaturated DOPC) and cholesterol. On the microsecond timescale we observe inhomogeneous mixing, with the saturated and unsaturated lipids showing preferential self-interaction. This simulation of the early stages of domain formation provides insight into the interactions that favor lateral domains, the dynamics of lateral separation, and the molecular-level structure and biophysical properties of the lateral domain.