(578f) Molecular Dynamics Simulations of Liquid-Condensed (LC) – Liquid-Expanded (LE) Phase Transformations in Model Lung Surfactant Monolayers

We present a systematic molecular dynamics study of liquid-condensed (LC) ? liquid-expanded (LE) phase transformations in multi-component model lung surfactant monolayers. The MARTINI coarse-grained force field is used to simulate monolayers containing pure dipalmitoylphosphatidylcholine (DPPC) and DPPC mixed with palmitoyloleoylphosphatidylcholine (POPC), cholesterol, or lung surfactant protein fragment SP-B_1-25. Our analysis of DPPC monolayers suggests that the LC phase forms via a nucleation and growth mechanism analogous to that observed in lipid bilayers. In the reverse process, the melting of the LC phase is observed to originate at defects in the monolayer. Both POPC and SP-B_1-25 are found to fluidize the monolayer. In agreement with experimental observations, SP-B_1-25 is found to reside in the LE phase of the monolayer and to perturb the packing of the surrounding lipids leading to local fluidization of the monolayer. The presence of POPC spread throughout a 1:1 DPPC:POPC monolayer prohibits DPPC condensed phase domains from nucleating at higher temperatures. At low temperatures both POPC and DPPC condense. Segregation of the two phospholipids is observed in the condensed phase, but not in the expanded phase. DPPC-cholesterol monolayers are found to display a phase of intermediate order, possibly the liquid-disordered (Ld) phase. The hysteresis loop for DPPC-cholesterol monolayers is shifted up slightly relative to that for pure DPPC, suggesting that the addition of cholesterol results in an increase in the transition temperature and stabilization of the condensed phase. Cholesterol is also observed to show a preference for the interface between the ordered and disordered phospholipids. Plots of temperature vs. order parameter reveal that DPPC displays substantial hysteresis, which is decreased by the addition of cholesterol or POPC and is abolished altogether by addition of SP-B_1-25, which nucleates disorder causing the disappearance of the ordered side of the hysteresis loop. These results illustrate that coarse-grained molecular dynamics simulation is a powerful tool for making qualitative observations of the dynamic phase behavior of lipid and lipid-peptide monolayers on a length-scales not accessible by experimental methods or atomistic simulation.