The research proposed in this application is carried out with the objective of obtaiing basic information which can be used to build an understanding in molecular terms of phy siologically important biological membrane phenomena. Work is centered on the continuing investigation of the interactions between lipids in multicomponent bilayers and between lipid and protein components in these systems. Of special interest are multicomponent bilayers exhibiting compositional domain structures wither within the plane of the bilayer or between its apposing faces. The research is specifically aimed at answering the following questions. (1) What factors result in compositionally asymmetric bilayers? (2) What are the properties of bilayers with asymmetric distributions of lipids? (3) What are the conditions governing in-plane compositional domain formation? (4) What are the properties of such systems? (5) What are the factors governing lipid-protein interactions in bilayers? The bilayer systems employed in this work are primarily unilamellar bilayer vesicles of minimum diameter (about 200 Angstrom) and large unilamellar vesicles with diameters greater than 400 Angstrom. Glycerol based lipids are of primary concern. Interactant proteins include cy tochrome b5, the G protein of vesicular stomatitis virus and analogs of this type of intrinsic membrane protein made by semi-synthesis. Assessment of the parameters governing interactions between components and the properties of compositional domain systems will depend upon a variety of physical techniques including fluorescence, NMR (1H, 13C and 31P), photon correlation spectroscopy, differential scanning calorimetry and hy drodynamic methods.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM014628-24
Application #
3268660
Study Section
Biophysics and Biophysical Chemistry B Study Section (BBCB)
Project Start
1977-05-01
Project End
1992-04-30
Budget Start
1989-05-01
Budget End
1990-04-30
Support Year
24
Fiscal Year
1989
Total Cost
Indirect Cost
Name
University of Virginia
Department
Type
Schools of Medicine
DUNS #
001910777
City
Charlottesville
State
VA
Country
United States
Zip Code
22904
Sankaram, M B; Jones, J D (1994) Mode of membrane interaction of wild-type and mutant signal peptides of the Escherichia coli outer membrane protein A. J Biol Chem 269:23477-83
Sankaram, M B; Marsh, D; Gierasch, L M et al. (1994) Reorganization of lipid domain structure in membranes by a transmembrane peptide: an ESR spin label study on the effect of the Escherichia coli outer membrane protein A signal peptide on the fluid lipid domain connectivity in binary mixtures of dimyristoy Biophys J 66:1959-68
Moll, T S; Thompson, T E (1994) Semisynthetic proteins: model systems for the study of the insertion of hydrophobic peptides into preformed lipid bilayers. Biochemistry 33:15469-82
Almeida, P F; Vaz, W L; Thompson, T E (1993) Percolation and diffusion in three-component lipid bilayers: effect of cholesterol on an equimolar mixture of two phosphatidylcholines. Biophys J 64:399-412
Almeida, P F; Vaz, W L; Thompson, T E (1992) Lateral diffusion and percolation in two-phase, two-component lipid bilayers. Topology of the solid-phase domains in-plane and across the lipid bilayer. Biochemistry 31:7198-210
Sankaram, M B; Thompson, T E (1992) Deuterium magnetic resonance study of phase equilibria and membrane thickness in binary phospholipid mixed bilayers. Biochemistry 31:8258-68
Melo, E C; Lourtie, I M; Sankaram, M B et al. (1992) Effects of domain connection and disconnection on the yields of in-plane bimolecular reactions in membranes. Biophys J 63:1506-12
Sankaram, M B; Marsh, D; Thompson, T E (1992) Determination of fluid and gel domain sizes in two-component, two-phase lipid bilayers. An electron spin resonance spin label study. Biophys J 63:340-9
Wimley, W C; Thompson, T E (1991) Phosphatidylethanolamine enhances the concentration-dependent exchange of phospholipids between bilayers. Biochemistry 30:4200-4
Sankaram, M B; Thompson, T E (1991) Cholesterol-induced fluid-phase immiscibility in membranes. Proc Natl Acad Sci U S A 88:8686-90

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