LIPIDPROD - Lipid-protein interactions in membrane organisation

• Antragstellerinnen / Antragsteller: Professorin Dr. Petra Schwille; Professor Dr. Kai Simons
• Fachliche Zuordnung: Biophysik
• Förderung: Förderung von 2009 bis 2012
• Projektkennung: Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 128127235

Membranes are central to understand cellular organization and function. However, the lipid bilayer, which constitutes the fluid matrix of the membrane, was for years neglected and considered to be a mere solvent for the proteins associated with the membrane. This view changed with the increasing awareness of the complexity of the lipid composition of bilayers. Eukaryotic membrane lipids are glycerophospholipids, sphingolipids, and sterols and it is thought that more than 1,000 different lipid species are present in mammalian cells. Why there are so many lipids in cell membranes is not understood.Another promoter of bilayer research was the introduction of the lipid raft concept to subcompartmentalize cell membranes. This concept suggests that cell membranes containing sphingolipids, saturated phosphatidylcholine and cholesterol are occupied by fluctuating nanoscale assembles that are poised for coalescence into larger scale, more stable domains (including some and excluding other proteins) that are postulated to function for membrane trafficking and signaling.The objectives of this CRP are to understand:1. The spatial, nanoscopic, organization of both lipid-anchored and transmembrane proteins within membranes of live cells with special emphasis on proteins that have been claimed to be raft-associated.2. How these nanoscopic membrane protein assemblies can associate to generate more stable raft platforms with additional functions.3. How membrane proteins interact with the different lipid species and how lipid-protein interactions contribute to membrane function. One specific issue will be to analyze how transmembrane proteins become “raftophilic”.4. Studies in cells will be complemented by reconstitution studies of selected proteins using simplified model systems such as Giant Unilamelar Vesicles. The goal will be to find the lipid requirements for association with-raft domain.5. To develop methodology to simulate and model the interplay of lipids and proteins over a multitude of scales in time and space.

• DFG-Verfahren: Sachbeihilfen