Molecular Dynamics Simulations of Liquid Condensed to Liquid Expanded Transitions in DPPC Monolayers

Phospholipids are the main building blocks of cell membranes,and play a major role in several biological processes such as theregulation of the surface tension of the air-alveolar interface,essential to breathing. Dipalmitoyl-phosphatidylcholine (DPPC),the major component of pulmonary surfactant (~40wt%), is able toform a tightly packed gel phase when compressed at physiologicaltemperatures and reduce the surface tension to near-zero values.1Thus, understanding the response of DPPC to changes in surfacearea is fundamental to determining the functionality of lungsurfactant and how to better design lung surfactant replacementsfor respiratory distress syndrome, both neonatal and adult.It is well known that DPPC, exhibits a liquid-condensed (LC) toliquid-expanded (LE) transition. Despite the considerable amountof experimental work on the surface-pressure isotherm of DPPC,there is still certain degree of uncertainty regarding the trueisotherm. Duncan and Larson2 have reviewed this situation in anextensive article.Development of accurate force fields, has advanced considerablythe application of computer simulations to investigatephospholipid films. In comparison to bilayers, less studies havebeen devoted to phospholipid monolayers3, 4 and just a few haveaddressed the computation of the pressure-area isotherm.More recent work, indicates that very long simulation times, atleast tens of nanoseconds, are necessary to enable the relaxation ofthe monolayer and formation of the liquid condensed phase.Simulations of the order of microseconds, have been achievedusing coarse grained models, where several sites of thephospholipid chain and the solvent are represented aspseudoatoms. To the best of our knowledge, there have not beenprevious attempts to investigate the LC-LE transition, through thecomputation of the pressure-area isotherm, using atomic models,where water and phospholipids are modelled explicitly.