"Lipid raft" formation: Experiments and mathematical modelling

Linda Cummings (Nottingham)

There is great biological interest currently in so-called "lipid rafts", lipid/protein microdomain structures, enriched in cholesterol and sphingomyelin, that are observed within eukaryotic cell membranes. As (essentially) phase-separated regions within the 2D cell membrane it is thought that "rafts" can recruit certain reactants (e.g. proteins) and prevent their interaction with other reactants in the rest of the membrane, or conversely, bring desired reactants into close proximity, thus promoting certain reactions. Moreover, rafts are implicated in the mechanism of virus entry into cells, and in many cell-signalling processes, and so are the focus of much current research activity. Thus, lipid rafts are thought to play many important roles in cell biology, but the basic principles that govern their formation and function remain poorly understood.

Since real cells are difficult to probe and enormously complicated, raft formation and disassembly may be studied in model lipid bilayers. We study the simplest model system of a bilayer composed of cholesterol and phosphatidylcholine (PC). The formation of cholesterol-enriched regions (the "rafts") is monitored using fluorescence microscopy. We propose a mathematical model for the raft formation, based on considerations of the interactions and bond formations between individual cholesterol molecules. Results of the mathematical model are compared to the experimental system, and very good agreement is found. We discuss the implications of our findings, and directions for future work.

Collaboration with Giles Richardson, Helen Harris, and Paul O'Shea (Nottingham)