Molecular View of Phase Coexistence in Model Membranes

Abstract

We used computer simulations to investigate phase transformations in lipid monolayers. This is important for understanding lipid-lipid interactions underlying lateral organization in biological membranes, and the role of phase coexistence in the regulation of surface tension by lung surfactant. Molecular dynamics simulations with the coarse-grained force field MARTINI were employed to achieve large length (∼80 nm in lateral dimension) and time (tens of microseconds) scales. Lipid mixtures containing saturated and unsaturated lipids and cholesterol were investigated under varying surface tension and temperature. We reproduced compositional lipid de-mixing and transformation into liquid-expanded (LE) and liquid-condensed (LC) phases, and into liquid-ordered (Lo) and liquid-disordered (Ld) phases. Transformation proceeded via either nucleation and growth, or spinodal decomposition, with distinct coarsening kinetics. Nucleation rate and growth exponents were calculated. Partial lipid areas and phase composition showed a different dependence on surface tension. The domain boundary length increased and the line tension decreased with reducing surface tension. Domains of Lo phase manifested spontaneous curvature at low surface tensions. The surface viscosity of monolayers with phase coexistence increased due to domain re-organization under shear. In the Lo/Ld mixture, strong compositional fluctuations were observed at higher temperatures. Monolayer collapse occurred in the disordered phase (LE or Ld), which then transferred into bilayer folds and monolayer-bilayer connection. Domains of coexisting phased either increased or reduced monolayer stability. We also investigated lipid bilayers of the same composition. Decreasing surface tension in monolayers and temperature in bilayers had similar effects on the properties of coexisting phases.