Theoretical Approach to Organization and Function of Biological Membranes

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TECHNICAL SUMMARY:This award supports theoretical research and education in biological physics. The research involves a series of increasingly sophisticated models of biological membranes which are designed to elucidate salient structure in the organization of molecules in the membrane. This idea, that molecules in the membrane of a cell are not distributed uniformly, underlies a set of new research questions. The underlying hypothesis is that the distribution of proteins and other molecules, such as cholesterol, in the cell membrane leads to functional organization, i.e. this organization can affect a host of other biologically important processes such as cell signaling, membrane fusion, viral entry and a variety of other functions which involve the cell membrane. Techniques of statistical mechanics and simulation will be used to explicate behaviors of model bilayer membranes consisting of cholesterol, saturated and unsaturated lipids with specific goal of observing the phase separation in this quasi-two dimensional fluid. Three specific phenomenon are highlighted in this research. The first attempts to identify sound theoretical basis for the existence (or nonexistence) and properties and dynamics of membrane rafts. Such rafts, described as regions of saturated lipids and cholesterol that had aggregated and float together. The functionality which is associated with rafts derives from the attachment of signaling proteins to the edges of the raft and thereby providing structural organization for signaling processes the couple the interior and exterior of the cell. NON-TECHNICAL SUMMARY:This award supports fundamental theoretical research and education on the biological physics of cell membranes. Scientific understanding of living cells has clearly shown that the cell membrane is complex and sophisticated in its functionality, doing far more than simply acting as a container holding the contents of the cell in place. With new understanding that the molecules that form the membrane are not entirely disorganized, there have developed a number of conjectures of how the intrinsic structure in a cell membrane may organize the way biological processes occur in the region where transport of signaling occur between the cell interior and its external environment. The research will employ tools of theoretical physics and use computer simulations to describe the organization of molecules in groups in the membrane. These tools allow researchers to establish what sort of structures can exist in the membrane and whether this pays an essential role in allowing the cell to carry out the essential life processes. A key concept of cell membrane organization is that the membrane includes floating groups of molecules which carry specialized signaling molecules or other proteins involved in allowing the cell to communicate with its environment.This research will be conducted with the full participation of graduate students, who will be trained in modern methods of theory and computer simulation as applicable to biological systems, preparing them for careers in science and biotechnology. Finally the research will be performed in collaboration with scientists from the US and abroad, strengthening and enriching the US physical community.