Off-lattice model for the phase behavior of lipid-cholesterol bilayers

Lipid bilayers exhibit a phase behavior that involves two distinct, but cou pled, order-disorder processes, one in terms of lipid-chain crystalline pac king (translational degrees of freedom) and the other in terms of lipid-cha in conformational ordering (internal degrees of freedom). Experiments and p revious approximate theories have suggested that cholesterol incorporated i nto lipid bilayers has different microscopic effects on lipid-chain packing and conformations and that cholesterol thereby leads to decoupling of the two ordering processes, manifested by a special equilibrium phase, "liquid- ordered phase," where bilayers are liquid (with translational disorder) but lipid chains are conformationally ordered. We present in this paper a micr oscopic model that describes this decoupling phenomena and which yields a p hase diagram consistent with experimental observations. The model is an off -lattice model based on a two-dimensional random triangulation algorithm an d represents lipid and cholesterol molecules by hard-core particles with in ternal (spin-type) degrees of freedom that have nearest-neighbor interactio ns. The phase equilibria described by the model, specifically in terms of p hase diagrams and structure factors characterizing different phases, are ca lculated by using several Monte Carlo simulation techniques, including hist ogram and thermodynamic reweighting techniques, finite-size scaling as well as non-Boltzmann sampling techniques (in order to overcome severe hysteres is effects associated with strongly first-order phase transitions). The res ults provide a consistent interpretation of the various phases of phospholi pid-cholesterol binary mixtures based on the microscopic dual action of cho lesterol on the lipid-chain degrees of freedom. In particular, a distinct s mall-scale structure of the liquid-ordered phase has been identified and ch aracterized. The generic nature of the model proposed holds a promise for a unifying description for a whole series of different lipid-sterol mixtures . [S1063-651X(99)09305-8].