Monolayer-Bilayer Transformations with Phase Coexistence

Abstract

Lateral compression of a lipid monolayer at an air/water interface increases its surface density and reduces surface tension. Reduction of surface tension is possible until a certain threshold, below which the monolayer becomes unstable at the interface and collapses. For homogeneous monolayers, collapse is known to proceed via wrinkling/buckling, followed by folding into bilayers in water. For heterogeneous monolayers with coexisting phases, the mechanism of collapse is not fully understood. The effect of phase separation on monolayer stability and the distribution of phases between the monolayer and bilayers as folds form and grow remain unclear.We used molecular dynamics simulations to investigate collapse of lipid monolayers with coexisting phases. The coarse-grained force field Martini was employed to achieve large length and time scales. We reproduced liquid-liquid and liquid-solid phase coexistence in monolayers of saturated and unsaturated lipids and cholesterol, and simulated monolayer collapse. The presence of solid domains allowed sustaining lower surface tensions, while the liquid-ordered domains decreased monolayer stability due to spontaneous curvature. Folds formed in the disordered phase in both cases; curved domains shifted nucleation sites towards the phase boundary. The disordered phase was preferentially squeezed-out into bilayers, in agreement with experiments. As a result, the composition and phase fractions were altered in monolayers in equilibrium with bilayers compared to flat monolayers at the same surface tension. Phase behavior of bilayers in turn depended on degree of monolayer compression. The monolayer-bilayer connection was highly enriched in unsaturated lipids. Percolation of solid domains slowed monolayer collapse below the equilibrium tension. The study is important in general for understanding the mechanism of folding of heterogeneous thin films and the role of lateral organizations in biological membranes, and is directly relevant for the function of lung surfactant.