A lattice model of ternary mixtures of lipids and cholesterol with tunable domain sizes

Much of our understanding of the physical mechanisms underlying the formation of raft domains in biological membranes is based on atomistic simulations of simple model systems, especially of ternary mixtures consisting of saturated and unsaturated lipids, and cholesterol. To explore the properties of such systems at macroscopically large scales, we here present a simple ternary mixture lattice model, involving a small number of nearest neighbor interaction terms. Monte Carlo simulations of mixtures with different compositions show an excellent agreement with experimental and atomistic simulation observations across multiple scale, ranging from the local distributions of lipids to the macroscopic phase diagram of the system. The simplicity of the model allows us to identify the roles played by the different interactions between components, and the interplay between them. Importantly, by changing the value of one of the model parameters, we can tune the size of the liquid ordered domains, thereby to simulate both Type II mixtures exhibiting macroscopic phase separation and Type I mixtures with nanoscopic domains which are considered as better models for lipid rafts. Both types of mixtures seem to fit the same generic low-temperature phase diagram, but in the latter case the identification of phase coexistence requires deeper analysis of the internal structure of the domains. Our model results suggest that short range packing is likely to be a key regulator of the stability and size distribution of raft domains in biological membranes that contain many lipid species with different melting temperatures.