Erwin London

Structure, organization, and function of membrane proteins and membrane lipids

Our group studies biomembrane structure and function by combining spectroscopic methods, especially fluorescence, as well as a combination of chemical, biochemical, cell biological and molecular biological approaches. In general, we are interested in determining how membranes are organized by lipid-lipid and lipid-protein interactions and how lipids influence membrane protein function.

Role of Sphingolipid-Cholesterol Lipid Domains (Rafts) in Membrane Organization and Its Influence Upon Membrane Protein Function

Highly ordered domains with tight lipid packing (rafts) are sphingolipid and cholesterol rich regions of biomembranes that contain a special subset of membrane proteins.  Rafts have critical roles in a variety of signal transduction and pathological processes, including viral and bacterial infection. We proposed (in collaboration with the Stony Brook lab of Dr. Deborah Brown) the now widely accepted hypothesis that rafts are tightly packed liquid ordered state domains, and defined many of the rules that govern raft formation and the association of particular lipids and proteins in rafts.  These studies are being extended to asymmetric membranes (see below).   

Lipid Exchange to Explore Biomembrane Organization and Membrane Protein Function

Natural membranes contain a bilayer of lipids that are often asymmetric, with different lipids in the inner and outer lipid monolayers.  Our lab developed a breakthrough method for facile production of asymmetric membranes by lipid exchange using lipids bound to cyclodextrins, water soluble cyclic glucose oligomers with a hydrophobic cavity that can accommodate the hydrocarbon chains of lipids.  By carrying lipids between lipid vesicles with different lipid compositions, we found the desired asymmetric vesicle can be prepared.  We have used this approach to study membrane domain formation in biologically-relevant asymmetric artificial membranes.  Recently, the lab extended the method to living cells, allowing facile and wide-ranging manipulation of the lipids in the plasma membrane of cells for the first time.  The method is being applied to understand how lipids control membrane protein function in living cells.