Simulation Study of Composition Fluctuations in Lipid Bilayers

Abstract

Lipid bilayers constitute the basis of biological membranes. Understanding lipid mixing and phase behavior can provide important insights into membrane lateral organization (the raft hypothesis). Here we investigate model lipid bilayers below and above the miscibility transition temperatures. Molecular dynamics simulations with the MARTINI coarse-grained force field are employed to model bilayers on a length scale approaching 100 nm laterally and a time scale of tens of microseconds. We simulate lipid mixtures containing saturated and unsaturated lipids, and cholesterol at different concentrations and temperatures between 270 and 340 K. The coexistence of liquid-crystalline and gel, as well as liquid-ordered and liquid-disordered phases is reproduced. We induce a gradual transition from phase separation to mixing by raising the temperature and adding hybrid lipids (with a saturated and an unsaturated chains). The evolution of bilayer properties along this transition is analyzed. Domain size and phase boundary length, the length and time scales of composition fluctuations, and inter-leaflet coupling are quantified. The results allow characterizing partitioning of hybrid lipids between the coexisting phases, their role in composition fluctuations, and also the effect of spontaneous curvature on composition fluctuations. Curved domains are observed in both symmetric and asymmetric bilayers (with different composition of the two leaflets).