Raft Registration Across Bilayers In a Molecularly Detailed Model

Membrane lateral heterogeneity is accepted as a requirement for the function of biological membranes. Coupling between bilayer leaflets plays an important role in biomembrane function inducing and registering rafts across leaflets for various cellular signals. Nevertheless registration mechanisms remain undetermined and several suggestions have been made: including chain interdigitation, cholesterol translocation in the case of lipids, interfacial energy, electrostatic coupling, van der Waals interactions and composition-curvature coupling. Recent experiments with mixtures of polymer amphiphiles that exhibit domain registration upon ligand-induced segregation suggest a general mechanism. We used coarse grained molecular dynamics (CGMD) simulations to show that raft registration arises spontaneously in bilayers upon segregation of a calcium or ligand-induced ordered phase from a liquid disordered phase. Thickness mismatching between phases induces a localized curvature change of the liquid phase which guides distant domains together and ultimately stabilizes the registered state. The absence of explicit charge in the model and the fact that domain size modulates the strength of transmembrane coupling demonstrate that collective interactions are sufficient to induce raft registration.