The basic components for synthesising, assembling and operating a higher life form come wrapped in a diaphanous, greasy film just nanometers thick. Only a decade ago many biologists regarded the eukaryotic cell’s external or plasma membrane as little more than a passive stage for the molecular theatre of life. Diagrams in biology texts represented the plasma membrane as simple bilayer of phospholipid molecules, oriented with hydrophobic heads pointing outwards and joined by their tails.

Associate Professor Katharina Gaus, head of the Cellular Membrane Biology Laboratory at the University of New South Wales Centre for Vascular Research, says the reality is very different: the plasma membrane is not homogeneous but a shifting mosaic of hundreds of different lipids that is actively involved in cell function. She believes the cell’s lipid ‘coat of many colours’ fine-tunes the functions of the multitude of protein molecules embedded in the plasma membrane: signalling receptors, ion channels, cell adhesion molecules and anchorage points for the internal cytoskeleton.

In 2003, Gaus was the lead author of a seminal paper in Proceedings of the National Academy of Science that reported the first direct visualisation of lipid rafts in cell membranes via high-resolution fluorescence microscopy. The lipid rafts consist of highly condensed patches of specific lipids such as cholesterol and sphingolipids. In white blood cells, semi-rigid rafts of cholesterol cover about 10 to 15 per cent of the cell surface. Membrane protrusions called filopodia, adhesion points and cell-to-cell contacts are highly enriched in the lipid rafts, suggesting that cell-membrane proteins are anchored within the lipid rafts, which influence their function.

Gaus will describe her group’s latest findings at the Australian Peptide Association’s annual conference, Peptide Australia 2008, held on Stradbroke Island in October.

“I’m very much a fundamental scientist,” says Gaus. “I’m trying to understand the cell membrane at the level of processes that occur within it rather than in terms of the structure and function of individual molecules. Before 2003, much of the debate around lipid rafts was around whether they existed and, if so, how they could be characterised, and what technology was needed to do that.

“The debate became almost academic, and revolved around semantics: if such an entity existed, could it be called a lipid raft or something else. It wasn’t really advancing the field. So we tried to step outside the debate and ask whether membrane organisation influenced protein function, as had been postulated. We set out to link particular membrane domains to specific cell functions, such as T cell activation in an immune response.

“We started by setting up mass spectrometry to characterise every lipid, then devised experiments to determine whether manipulating cholesterol levels in the cell changed the abundance of other lipids. Did changing one lipid change the abundance of other lipids? And how does that change membrane domains and, as a consequence, T cell signalling?

“It was a bean-counting exercise, but we needed information on the abundance of various lipids and how they are distributed in the cell membrane, to understand how they might influence protein distribution and function.”