The proposed research program is directed to quantitatively characterize the lateral organization of molecules in biological membranes so that precise correlations can be established between membrane organization and membrane function. These studies will provide information concerning the disposition of molecules within lipid bilayer membranes in terms of the formation of clusters or domains of specific composition. These compositional domains will be characterized, using statistical thermodynamic methods, in terms of their size, number, geometry and topological localization within the membrane. The dependence of these molecular distributions on the composition, physical state of the bilayer and external physicochemical parameters like temperature, ionic strength, pH and the chemical composition of the medium will be assessed. These distributions will be obtained from the analysis of excess heat capacity functions and excess volume functions experimentally determined by scanning calorimetry and density measurements. The experimental studies will be performed in reconstituted membranes containing phosphatidylcholines, phosphatidylserines and glycosphingolipids (gangliosides and cerebrosides). The results of this research project will contribute to our understanding of the relationships between molecular organization and functional properties in biological membranes.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM037911-03
Application #
3293739
Study Section
Biophysics and Biophysical Chemistry B Study Section (BBCB)
Project Start
1986-07-01
Project End
1990-12-31
Budget Start
1988-01-01
Budget End
1988-12-31
Support Year
3
Fiscal Year
1988
Total Cost
Indirect Cost
Name
Johns Hopkins University
Department
Type
Schools of Arts and Sciences
DUNS #
045911138
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Johnson, C R; Angeletti, M; Pucciarelli, S et al. (1996) Oxygen binding to fallow-deer (Dama dama) hemoglobin: stepwise enthalpies at pH 7.4. Biophys Chem 59:107-17
Hilser, V J; Freire, E (1995) Quantitative analysis of conformational equilibrium using capillary electrophoresis: applications to protein folding. Anal Biochem 224:465-85
Freire, E (1995) Thermal denaturation methods in the study of protein folding. Methods Enzymol 259:144-68
Murphy, K P; Freire, E (1995) Thermodynamic strategies for rational protein and drug design. Pharm Biotechnol 7:219-41
Echabe, I; Haltia, T; Freire, E et al. (1995) Subunit III of cytochrome c oxidase influences the conformation of subunits I and II: an infrared study. Biochemistry 34:13565-9
Gomez, J; Hilser, V J; Xie, D et al. (1995) The heat capacity of proteins. Proteins 22:404-12
Murphy, K P; Freire, E; Paterson, Y (1995) Configurational effects in antibody-antigen interactions studied by microcalorimetry. Proteins 21:83-90
Johnson, C R; Morin, P E; Arrowsmith, C H et al. (1995) Thermodynamic analysis of the structural stability of the tetrameric oligomerization domain of p53 tumor suppressor. Biochemistry 34:5309-16
Freire, E (1995) Differential scanning calorimetry. Methods Mol Biol 40:191-218
Gomez, J; Freire, E (1995) Thermodynamic mapping of the inhibitor site of the aspartic protease endothiapepsin. J Mol Biol 252:337-50

Showing the most recent 10 out of 48 publications