Eduardo Mendez-Villuendas

Molecular View of Phase Coexistence in Lipid Monolayers

We used computer simulations to study the effect of phase separation on the properties of lipid monolayers. This is important for understanding the lipid-lipid interactions underlying lateral heterogeneity (rafts) in biological membranes and the role of domains in the regulation of surface tension by lung surfactant. Molecular dynamics simulations with the coarse-grained MARTINI force field were employed to model 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 demixing and the coexistence of liquid-expanded and liquid-condensed phases as well as liquid-ordered and liquid-disordered phases. Formation of the more ordered phase was induced by lowering the surface tension or temperature. Phase transformations occurred via either nucleation or spinodal decomposition. In nucleation, multiple domains formed initially and subsequently merged. Using cluster analysis combined with Voronoi tessellation, we characterized the partial areas of the lipids in each phase, the phase composition, the boundary length, and the line tension under varying surface tension. We calculated the growth exponents for nucleation and spinodal decomposition using a dynamical scaling hypothesis. At low surface tensions, liquid-ordered domains manifest spontaneous curvature. Lateral diffusion of lipids is significantly slower in the more ordered phase, as expected. The presence of domains increased the monolayer surface viscosity, in particular as a result of domain reorganization under shear.

Computer simulations of the phase separation in model membranes

We used computer simulations to investigate the properties of model lipid membranes with coexisting phases. This is relevant for understanding lipid-lipid interactions underlying lateral organization in biological membranes. Molecular dynamics simulations with the MARTINI coarse-grained force field were employed to study lipid bilayers -40 nm in lateral dimension on a 20 micros time scale. The simulations retain near atomic-level detail and lipid chemical specificity, and allow formation of multiple domains of tens of nanometers in size. Using ternary lipid mixtures of saturated and unsaturated lipids and cholesterol, we reproduced the coexistence of the Lalpha/gel phases and the Lo/Ld phases. Phase transformation proceeded by either nucleation or spinodal decomposition. The properties of coexisting phases were characterized in detail, including partial lipid areas, composition, phase boundary and domain registry, based on Voronoi tessellation. We investigated variations of these properties with temperature and surface tension, and compared them to our recent simulations of lipid monolayers of the same size and composition. We found substantial overlap in bilayer and monolayer properties. Increasing the temperature in bilayers produced similar effects as increasing the surface tension in monolayers. This information can be used for interpreting experimental data on model membranes.