A lattice model of ternary mixtures of lipids and cholesterol with tunable domain sizes (2203.03269v3)

Abstract: Much of our understanding of the physical properties of raft domains in biological membranes, and some insight into the mechanisms underlying their formation stem from atomistic simulations of simple model systems, especially ternary mixtures consisting of saturated and unsaturated lipids, and cholesterol (Chol). To explore the properties of such systems at large spatial 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 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. The Type II mixture simulation results fit well to the experimentally-determined phase diagram of mixtures containing saturated DPPC/unsaturated DOPC/Chol. When the tunable parameter is changed, we obtain the Type I version of DPPC/DOPC/Chol, i.e., a mixture not showing thermodynamic phase transitions but one that may be fitted to the same phase diagram if local measures are used to distinguish between the different states. Our model results suggest that short range packing is likely to be a key regulator of the stability and size distribution of biological rafts.