This year’s International AIDS Conference outlined ambitious global treatment goals with the potential to save millions of lives. On the downside, however, participants reported disappointingly slow progress toward an effective vaccine against HIV.
According to David Gidalevitz, IIT associate professor of physics, a more fundamental understanding of cell membranes—the port of entry for HIV and other pathogens—may eventually break this deadlock. His research into the nature of biological membranes, reported in the journal Physical Review Letters, is providing important new insights into these dynamic structures.
“In living cells, we see curvature everywhere,” Gidalevitz says, noting that it occurs not only on the cell’s surface, but in internal structures. “But what is the mechanism of this curvature? That’s a very interesting question.”
The new paper examines the role of cholesterol in directing cell membrane curvature in the presence of gp41—a key HIV fusion protein, which acts like a molecular harpoon, piercing the cell membrane and initiating HIV infection.
To study membrane behavior, Gidalevitz created an artificial monolayer—a thin film of lipids (including cholesterol)—on the surface of water. The advantage of this model membrane is that it permits extremely fine control over the process. “We can determine the amount of molecules at the water interface to a very high degree,” he says.
While it has long been known that proteins can affect the curvature of the cell membranes with which they interact, the new study demonstrated for the first time that cholesterol concentration also affects protein shape.
In the case of gp41, the presence of cholesterol causes the protein to assume one of two conformational forms—alpha helix (when cholesterol is low) or beta sheet (when it is high), which also changes how deeply the HIV protein penetrates the cell membrane.
Gidalevitz believes that understanding the subtleties of membrane-protein interaction is an essential piece of the HIV puzzle and will ultimately assist efforts to outwit the virus.
This research was supported by the National Institutes of Health, the Defense Advanced Research Projects Agency, and the Department of Energy
Driving Membrane Curvature: www.aps.anl.gov/Science/Highlights/Content/APS_SCIENCE_20120613.php