Research Description |
We are interested in the physical and chemical properties of biomembranes. This bilayer state of matter poses both experimental and conceptual challenges. Our goal is to understand the interactions that control the tendency of each component of the membrane bilayer to cluster, to change phase, to transfer to another membrane, or to chemically react. Thus, the thermodynamics of mixing plays a key role for interpreting our experiments and calculations.
The biomembrane can be considered as a nonrandom mixture of lipids and proteins. Some components, such as phosphatidylserine or cholesterol, can induce separated fluid bilayer phases within the biomembrane. The cholesterol-rich phase is particularly fascinating, because it is as highly ordered as a crystal, yet is actually a fluid bilayer.
Our laboratory uses a variety of chemical and physical techniques to study real and model biomembranes. We synthesize various kinds of phospholipids, including spin-labeled, fluorophor-labeled, and perdeuterated phospholipids. We use nuclear magnetic resonance and electron spin resonance spectroscopies to examine the state of motion and order in the bilayer. Light-scattering, optical microscopy, and X-ray diffraction enable detection and identification of different lipid phases. We use various fluorescence spectroscopic methods, especially fluorescence quenching, to study bilayer behavior and partition of lipids or proteins between coexisting membrane phases.
Recently, we have been able to describe the phase diagram of a 3-component bilayer mixture that is a reasonable model for mammalian plasma membranes, DPPC/DLPC/cholesterol. Understanding this phase behavior required experiments using confocal fluorescence microscopy, fluorescence resonance energy transfer, and pyrene excimer/monomer ratios. A surprising result is that some regions of the diagram show nano-scale "phase" separation that might be related to the so-called lipid rafts postulated to exist in plasma membranes. |
Publications |
Feigenson, G.W. 2007. Phase Boundaries and Biological Membranes. Annu.Rev.Biophys.Biomol.Struct. 36:63-77.
Baumgart, T., Hunt, G., Farkas, E.R., Webb, W.W., and Feigenson, G.W. 2007. Fluorescence probe partitioning between Lo/Ld phases in lipid membranes. Biochim. Biophys. Acta 1768:2182-2194.
Zhao, J., Wu, J, Heberle, F.A., Mills, T.T., Klawitter, P., Huang, G. Costanza, G. and Feigenson, G.W. 2007. Phase studies of model biomembranes: Complex behavior of DSPC/DOPC/Cholesterol. Biochim. Biophys. Acta, 1768: 2764-2776.
Zhao, J., Wu, J, Shao, H. Kong, F., Jain, N., Hunt, G. and Feigenson, G.W. 2007. Phase studies of model biomembranes: Macroscopic coexistence of L_+L_, with light-induced coexistence of L_+Lo Phases. Biochim. Biophys. Acta, 1768: 2777-2786.
van Meer, G., Voelker, D.R. and Feigenson, G.W. 2008. Membrane lipids: where they are and how they behave. Nature Reviews 9:112-124.
Mills, T.T., Toombes, G.E.S., Tristram-Nagle, T., Heberle, F.A., Morales, N., Zhao, J. Wu, J., Toombes, G.E.S.,Nagle, J.F. and Feigenson, G.W. 2008. Orientational Order Parameters and Areas in Fluid-Phase Oriented Lipid Membranes Using Wide Angle X-ray Scattering. Biophys. J. 95: 669-681.
Mills, T.T., Tristram-Nagle, T., Heberle, F.A., Morales, N., Zhao, J. Wu, J., Toombes, G.E.S., Nagle, J.F. and Feigenson, G.W. 2008. A New Method for Finding Phase Separation: WAXS Detects Liquid Domains in Oriented DOPC/DPPC/Cholesterol Membranes. Biophys. J. 95: 682-690.
Click here for Dr. Feigenson's PubMed listing. |