Molecular dynamics simulation of phase transitions in model lung surfactant monolayers

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-B(1-25), the ordered side of the hysteresis loop is abolished altogether, suggesting that SP-B(1-25) effectively nucleates disorder in the monolayer on heating. SP-B(1-25) 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.