Rafts as Curvature-Induced Microemulsions

University Of Washington, Seattle WA

Investigators

Abstract

TECHNICAL SUMMARY This award supports theoretical research and education to investigate physical mechanisms leading to the organization of lipid membranes. The idea that the plasma membrane is not uniform but displays physical organization which leads to functional organization is one that has attracted enormous attention. This is due to the fact that such organization would affect a host of biologically important processes, such as signaling, endocytosis, membrane fusion, and viral entry, among many others. In spite of the compelling nature of the hypothesis, and of the ever-increasing evidence, there remains skepticism concerning the idea. The PI will investigate a mechanism that arises from the well-known variety in lipid composition of the inner and outer leaves of the plasma membrane. It has been hypothesized that differences in composition between the leaves can couple to the curvature of the membrane, with unsaturated lipids preferring regions in which the membrane bulges outward, and saturated lipids and cholesterol preferring regions on the opposite leaf where the membrane bulges inward. It was known that such coupling can, in principle, bring about modulated phases, such as those displaying alternating stripes. But these phases are not seen in biological systems. These same forces can also induce a curvature-induced microemulsion, with droplets whose area is characterized by the ratio of the bending modulus to the surface tension. These droplets would form and break up dynamically. The PI will use theoretical and computational methods to develop this idea and to enable experimentalists to test the existence of such two-dimensional microemulsions. NONTECHNICAL SUMMARY This award supports theoretical research and education to investigate a physical mechanism for how the molecules in cell walls organize themselves. Proteins are the machines which carry out innumerable crucial functions in our body. Some are found on the outside of cells, others on the inside. In general it takes many different proteins working together to carry out some particular function. How do proteins on one side of the cell wall communicate with one another, and how do they communicate with proteins on the other side of the cell wall? It used to be thought that the proteins were distributed randomly over the cell surface so it was only by chance meetings that they found one another. And for a protein on one side of the cell wall to be positioned near one on the opposite side, that too was a matter of chance. More recently it has been suggested that this picture is incorrect. Instead it has been proposed that the molecules which make up the cell wall form distinct regions; the molecules with carbon tails that have no double bonds, like 'saturated fats,' form small regions with the molecule cholesterol. These regions float like rafts in a sea of molecules with carbon tails that do have double bonds, like 'unsaturated fats.' Proteins on either side of the cell wall are anchored to it, and these anchors can distinguish the rafts from the sea, and prefer to be in one or the other. In this picture, then, the distribution of proteins is not random; those that prefer the rafts are close together as are those that prefer the sea. This is very appealing but it leaves open one important question; why do these molecules aggregate into rafts and sea in the first place? The PI and collaborators are exploring the idea that undulations of the cell wall tend to organize the molecules comprising it much as waves in the ocean affect the seaweed floating on it, driving them apart at wave crests and pushing them together at wave troughs.