Atom-scale molecular interactions in lipid raft mixtures.

We review the relationship between molecular interactions and the properties of lipid environments. A specific focus is given on bilayers which contain sphingomyelin (SM) and sterols due to their essential role for the formation of lipid rafts. The discussion is based on recent atom-scale molecular dynamics simulations, complemented by extensive comparison to experimental data. The discussion is divided into four sections. The first part investigates the properties of one-component SM bilayers and compares them to bilayers with phosphatidylcholine (PC), the focus being on a detailed analysis of the hydrogen bonding network in the two bilayers. The second part deals with binary mixtures of sterols with either SM or PC. The results show how the membrane properties may vary substantially depending on the sterol and SM type available, the membrane order and interdigitation being just two of the many examples of this issue. The third part concentrates on the specificity of intermolecular interactions in three-component mixtures of SM, PC and cholesterol (CHOL) under conditions where the concentrations of SM and CHOL are dilute with respect to that of PC. The results show how SM and CHOL favor one another, thus acting as nucleation sites for the formation of highly ordered nanosized domains. Finally, the fourth part discusses the large-scale properties of raft-like membrane environments and compares them to the properties of non-raft membranes. The differences turn out to be substantial. As a particularly intriguing example of this, the lateral pressure profiles of raft-like and non-raft systems indicate that the lipid composition of membrane domains may have a major impact on membrane protein activation.