Studies of Phase Transition(s) in Phospholipid/Cholesterol Systems by Molecular Dynamics Simulations

Abstract

Molecular dynamics simulations of atomistic models show the ordering and condensing effect of the cholesterol on phospholipid bilayers. Such simulations are, however, too time consuming to permit monitoring of the gel/liquid crystalline phase transition. We used therefore the simplified coarse grained MARTINI model to study the phase transition in dipalmitoylphosphatidylcholine (DPPC) cholesterol mixtures. A recent study by Marrink shows that this model is able to describe the main phase transition of pure phospholipid systems reasonably. The area per molecule was calculated separately for the phospholipids and cholesterol as a partial specific area (Edholm & Nagle). The condensation effect of cholesterol is obtained with the atomistic model as a negative partial specific area for cholesterol. The coarse grained model reproduce the condensation effect and gives a negative partial specific area of cholesterol molecule at low cholesterol concentration and low temperatures above the main phase transition. The main phase transition occurs already at about 295K for the coarse grained model. There is, however, another (second order) phase transition at 304K, where partial specific area suddenly becomes positive for all cholesterol concentrations. Such a transition was, however, not observed with the atomistic model. A similar transition was observed in the order parameter versus temperature at low cholesterol concentration, but this vanishes at high concentration. These results were used to test different suggested relations between area per lipid and the order parameter. Below, the main transition, the radial distribution functions and chain order parameters were used to monitor the difference between long range positional order and chain order as well as to search for inhomogeneities in the lipid distribution.