Molecular dynamics simulations of lung surfactant lipid monolayers

Pulmonary surfactant provides for a lipid rich film at the lung air-water interface, which prevents alveolar collapse at the end of expiration. The films are likely enriched in the major surfactant component dipalmitoylphosphatidylcholine (DPPC), which, due to its saturated fatty acid chains, can withstand high surface pressures up to 70 mN/m, thereby reducing surface tension in that interface to very low values (close to 1 mN/m). Despite many experimental measurements in situ, as well as in vitro for native lung surfactant films, the exact mechanism by which other fluid lipid components of surfactant, in combination with surfactant proteins, allow for such low surface tension values to be reached is not well understood. We have performed molecular dynamics simulation of films composed of DPPC alone and in mixtures with other fluid and acidic lipid components of surfactant at the high densities relevant to the low surface tension regime. 10-50 ns simulations were performed with the software GROMACS, with 40-64 lipids molecules plus water, using 5 different lipid compositions and 7 different areas per lipid. The primary focus was to learn how differences in lipid composition affect the response of the monolayer to compression, such as the development of curvature or the loss of lipids to the exterior of the monolayer. The systems studied exhibit features of two of the major schools of thought of lung surfactant mechanisms, in that although unsaturated lipids did not appear to prevent the monolayers from achieving high surface pressure, POPG did appear to be selectively squeezed out of the DPPC/POPG monolayers at high lipid densities.