Physics Special Colloquium, January 18, 2005

Physical Forces in Biological Membranes

Horia I. Petrache

NICHD

Shielding the cell interior from the outside world, biological membranes support critical biological functions of cell defense, communication, and proliferation. Long thought to be passive hosts of membrane proteins, lipid bilayers are now recognized as key structural and mechanical participants in biomembrane functions. By setting physical parameters of rigidity, fluctuation, and lateral stress, lipids act on membrane channels, receptors, and signaling molecules. The physical parameters of lipids have been associated with health benefits, from prevention of cancer and heart disease to stabilization of normal brain function. Charged phosphatidylserine headgroups, polyunsaturated (omega-3 and omega-6) acyl chains and cholesterol have attracted special attention.

We have investigated these systems by X-ray diffraction and NMR spectroscopy to accurately determine membrane thicknesses and cross-sectional areas, structural parameters critical to evaluation of intra and interbilayer forces. In essence liquid-crystals, lipid bilayers fluctuate through compression and bending modes resulting in entropic repulsive forces. Combined with atomic-level computer simulations, measurements of membrane fluctuations by line-shape analysis of x-ray and NMR spectra complement the measurements of average structural parameters. This combination opens new approaches to the statistical mechanics and thermodynamics of biomembranes.

We have shown that lipid headgroup substitutions, polyunsaturation of acyl chains, and addition of cholesterol modify the balance of forces within biomembranes and introduce curvature stress. Quantified by modification of lateral compressibility and bending rigidity, these stresses are large enough to shift activation energies of membrane receptors, to alter membrane architecture, and to control membrane fusion.

By documenting universal physical laws of lipid packing, we have begun to rationalize the perplexing diversity of lipids in cellular membranes and lipid interactions with membrane receptors, channel and bathing solutions. By understanding inter and intrabilayer interactions, we can ultimately construct a solid physical basis for membrane processes such as signal transduction, protein trafficking, egg fertilization, and viral fusion.

10:30 a.m., Smith Laboratory, Room 1094

Refreshments served in Smith 1094 at 10:00 a.m.