In silico phase separation in the presence of GM1 in ternary and quaternary lipid bilayers

Cell membranes are multi-component mixtures with structural and compositional heterogeneity exhibiting a complex phase behavior. Domains formed in cell membranes often known as “Rafts” are of immense importance. Using coarse grained molecular dynamics simulations, we have studied the spontaneous phase separation of the ternary (POPC [1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine]/cholesterol/GM1) and quaternary (POPC/PSM[palmitoyl sphingomyelin]/cholesterol/GM1) lipid bilayers into liquid ordered (Lo) and liquid disordered (Ld) domains due to self-aggregation of GM1 molecules and co-localization of cholesterol with GM1 in accordance with experiments. It is found that GM1 molecules have the ability to associate strongly with each other which leads to the formation of ordered domains in the lipid mixture and the interactions are through the head group and unsaturated tails present in GM1. Preference of cholesterol for association with GM1 over PSM is observed, the domains consisting of GM1 and cholesterol are formed even in the presence of PSM. PSM also forms small domains with cholesterol that are randomly distributed in the Ld phase. Estimation of dynamic quantities like diffusion coefficient also shows that cholesterol has the highest diffusion rate in the Ld phase which is further attributed to its flip flop ability. It is found that in the presence of PSM, cholesterol can undergo flip flop even in the Lo phase. This is accredited to the interaction of cholesterol with PSM from which it can be concluded that in the presence of PSM, the domains formed by GM1 are less tightly packed and less stable than that in the ternary mixture.