The Role of Domains and Proteins in the Function of Lung Surfactant

Abstract

Lung surfactant forms a thin film at the gas exchange interface in alveoli. The film reduces the surface tension which is necessary for breathing. The film consists of a monolayer at the air/water interface connected with bilayer reservoirs in water. Lung surfactant is composed of a mixture of saturated and unsaturated, zwitterionic and anionic lipids; surfactant proteins B (SP-B) and C are associated with the interface. Surfactant proteins facilitate adsorption of lipids to the interface likely via stalk-like intermediates. The proteins are also believed to induce monolayer collapse by creating nucleation sites/fluidizing effect. Lipid components in monolayer segregate into domains of coexisting phases, which is suggested to increase monolayer stability. However, the exact mechanisms of these effects are still not fully understood.We study the role of phase coexistence and proteins in the function of lung surfactant. Molecular dynamics simulations with the coarse-grained model MARTINI are employed. We simulate mixtures of saturated and unsaturated phosphatidylcholine and phosphatidylglycerol lipids, cholesterol and SP-B proteins. The model of SP-B is built based on homology with the saposin family and was shown previously to mediate early stages of vesicle fusion [S Baoukina, DP Tieleman, Biophys J, 2010]. We reproduce phase separation into liquid-expanded (LE) and liquid-condensed (LC) or liquid ordered (Lo) phases in monolayers. SP-B partitions into the LE phase and prevents formation of the LC phase at conditions close to the phase transition. The protein also enhances lipid de-mixing. SP-B dimers induce bilayer folds in monolayers at positive surface tensions below the equilibrium spreading value. Monolayer collapse is initiated from the LE phase, and the composition of bilayer folds differs from the monolayer. SP-B anchors monolayers and bilayers and promotes lipid transfer.