Physical chemistry in biological membranes: resolving the chemical details of cell signaling

The chemical interactions that drive biological function operate in a complex environment. This is especially true of the plasma membrane, where cells present an array of chemical receptors that transmit environmental cues inside the cell. The spatial and temporal arrangement of these receptors from the nanometer to micrometer length scale is critical to function, but the chemical forces driving this organization are not well understood. Membrane protein dimerization, for example, is a key regulator of many receptor pathways, but its role in others is still controversial or completely unknown. Assembly of receptor complexes upon ligand stimulation is central to many signaling pathways, but the activation mechanisms are still poorly understood. Finally, lipid-protein interactions play many structural and regulatory roles in receptor activation, but they are difficult to study in functioning membranes. I will describe two recent projects in my group. In one project we investigate membrane protein interactions in live cells using PIE-FCCS and related methods. These efforts have led to several key insights into the organization and activation mechanism of receptors like plexins, growth factor receptors, and visual photoreceptors. The second project is to resolve the details of lipid-protein coupling in model membranes to build a more complete picture of the chemical landscape that governs cell communication.