Presence and Role of Midplane Cholesterol in Lipid Bilayers Containing Registered or Antiregistered Phase Domains.

Three-component lipid mixtures can produce coexisting liquid ordered and liquid disordered phases, a model for eukaryotic plasma membrane rafts. In compositionally symmetric bilayers with two phase-separated leaflets, phase domains of the two leaflets may align through registration, where domains are found across from domains of the same phase, or else antiregistration, where domains are found across from domains of the opposite phase. This alignment could serve as a method of information communication across the plasma membrane. We used coarse-grained molecular dynamics simulations to study ternary mixtures of a high-melting-temperature phospholipid, a low-melting-temperature phospholipid, and cholesterol. We found a significant presence of cholesterol molecules at the bilayer midplane rather than in a leaflet in some systems, corresponding to a lack of registration. Increasing the length of the acyl chains from 16 to 24 carbons in high-melting-temperature phospholipids or increasing the concentration of cholesterol from 20 to 35 mol % in the bilayer produced a transition from registration to antiregistration and gave rise to significant populations of midplane cholesterol.