Phase separation in biological membranes: integration of theory and experiment

Abstract

Lipid bilayer model membranes that contain a single lipid species can undergo transitions between ordered and disordered phases, and membranes that contain a mixture of lipid species can undergo phase separations. Studies of these transformations are of interest for what they can tell us about the interaction energies of lipid molecules of different species and conformations. Nanoscopic phases (<200 nm) can provide a model for membrane rafts, specialized membrane domains enriched in cholesterol and sphingomyelin, which are believed to have essential biological functions in cell membranes. Crucial questions are whether lipid nanodomains can exist in stable equilibrium in membranes and what is the distribution of their sizes and lifetimes in membranes of different composition. Theoretical methods have supplied much information on these questions, but better experimental methods are needed to detect and characterize nanodomains under normal membrane conditions. This review summarizes linkages between theoretical and experimental studies of phase separation in lipid bilayer model membranes.

Figure 1

Predicted and observed phenomena in lipid layers span broad length- and time-scales.

Figure 2

Analytical and simulation approaches span the range of lipid behavior, but simulating over the entire range remains a challenge.

Figure 3

Experimental techniques cover most of the range of lipid behavior, but still do not adequately determine nanodomain sizes and lifetimes.