Molecular dynamics simulation of phase transitions in model lung surfactant monolayers

Abstract

To explore the role of individual lung surfactant components in liquid-condensed (LC)/liquid-expanded (LE) phase transitions the MARTINI coarse-grained (CG) model is used to simulate monolayers containing DPPC and additional lipid or peptide components. Our analysis suggests that the LC phase forms from the LE phase via a nucleation and growth mechanism, while the LC–LE transition occurs by melting that originates from defects in the monolayer. On the time scale of our simulations, DPPC monolayers display a substantial hysteresis between the ordering and disordering transitions, which is decreased by the addition of a second component. In binary mixtures of DPPC with lung surfactant peptide fragment SP-B1–25, the ordered side of the hysteresis loop is abolished altogether, suggesting that SP-B1–25 effectively nucleates disorder in the monolayer on heating. SP-B1–25 is observed to perturb the packing of the surrounding lipids leading to local fluidization of the monolayer and to aggregate within the LE phase. In 1:1 DPPC:POPC monolayers, a high concentration of unsaturated phospholipid leads to a substantial decrease in the LC–LE and LE–LC transition temperatures. Adding cholesterol to pure DPPC increases the LC–LE and LE–LC transition temperatures and increases the order on the disordered side of the hysteresis loop leading to a phase of intermediate order, which could be the liquid-disordered (Ld) phase. Cholesterol is also observed to show a preference for LC–LE domain boundaries. The results of our molecular dynamics simulations coincide with many experimental observations and can help provide insight into the physiological roles of individual surfactant components.