Simulation Study of Domains in Lipid Monolayers

Abstract

Using computer simulations we investigated the effect of coexisting phases on the properties of lipid monolayers. This is important for understanding the role of domains in surface activity of monolayers in general, and specifically in regulation of surface tension by lung surfactant. Molecular dynamics simulations with the coarse-grained force field MARTINI were employed to study monolayers approaching 100 nm in lateral dimension on the time scale of tens of microseconds. Lipid mixtures containing saturated and unsaturated lipids and cholesterol were studied under varying surface tension (0-40 mN/m) and temperature (270-323 K). Compositional lipid de-mixing and coexistence of liquid-expanded and liquid-condensed phases as well as liquid-ordered and liquid-disordered phases was reproduced. Formation of the more ordered phase induced by lowering the surface tension or temperature occurred via either nucleation and growth or spinodal decomposition. Using cluster analysis combined with Voronoi tessellation we characterized in detail the properties of the phases and kinetics of domain growth. Area fraction and lipid composition of each phase, and boundary length were obtained as a function of temperature and surface tension. We also simulated lipid monolayers connected to bilayer reservoirs in water, which are relevant for the function of lung surfactant. The distribution of phases between the monolayers and bilayers, and the effect of domains on monolayer stability were determined.