X-ray diffraction studies will be performed with the aim of understanding the physical basis of membrane stability. Biomembranes contain a very diverse set of chemically distinct lipid species which contribute to the collective behavior of the bilayer in different ways. It is known that the phospholipids spontaneously assemble into a variety of bilayer and nonlamellar structures.
The aim of this research is to understand both the balance of colligative forces which stabilize bilayers in lieu of other structures and the way these forces arise from lipid chemical diversity.
Specific aims of the research include: 1) A model has been developed which explains lipid phase instability in terms of the spontaneous curvature elasticity of lipid layers. This model will be experimentally and theoretically refined and tested. Experiments will be performed to understand the way lipid diversity effects elastic properties. 2) It has been hypothesized that variations in the spontaneous curvature of different bilayer compositions affect the interaction and biodistribution of lipiphilic agents (e.g., oils, alcohols, anaesthetics, oligopeptides, and many drugs). Toward this end, the partitioning and destabilization effects of lipophilic agents will be studied. 3) New techniques of measuring membrane elastic properties will be explored. 4). The hydration potentials of lipid headgroups will be investigated. 5) The phase behavior and structure of novel membrane lipids and systems will be studied.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM032614-14
Application #
3281633
Study Section
Biophysical Chemistry Study Section (BBCB)
Project Start
1986-04-01
Project End
1995-03-31
Budget Start
1993-04-01
Budget End
1994-03-31
Support Year
14
Fiscal Year
1993
Total Cost
Indirect Cost
Name
Princeton University
Department
Type
Schools of Arts and Sciences
DUNS #
002484665
City
Princeton
State
NJ
Country
United States
Zip Code
08544
Mannock, David A; Collins, Marcus D; Kreichbaum, Manfried et al. (2007) The thermotropic phase behaviour and phase structure of a homologous series of racemic beta-D-galactosyl dialkylglycerols studied by differential scanning calorimetry and X-ray diffraction. Chem Phys Lipids 148:26-50
Mannock, D A; Lewis, R N; McElhaney, R N et al. (2001) An analysis of the relationship between fatty acid composition and the lamellar gel to liquid-crystalline and the lamellar to inverted nonlamellar phase transition temperatures of phosphatidylethanolamines and diacyl-alpha-D-glucosyl glycerols. Eur Biophys J 30:537-54
Harper, P E; Mannock, D A; Lewis, R N et al. (2001) X-ray diffraction structures of some phosphatidylethanolamine lamellar and inverted hexagonal phases. Biophys J 81:2693-706
Mannock, D A; Harper, P E; Gruner, S M et al. (2001) The physical properties of glycosyl diacylglycerols. Calorimetric, X-ray diffraction and Fourier transform spectroscopic studies of a homologous series of 1,2-di-O-acyl-3-O-(beta-D-galactopyranosyl)-sn-glycerols. Chem Phys Lipids 111:139-61
Keller, S L; Gruner, S M; Gawrisch, K (1996) Small concentrations of alamethicin induce a cubic phase in bulk phosphatidylethanolamine mixtures. Biochim Biophys Acta 1278:241-6
Lafleur, M; Bloom, M; Eikenberry, E F et al. (1996) Correlation between lipid plane curvature and lipid chain order. Biophys J 70:2747-57
Osterberg, F; Rilfors, L; Wieslander, A et al. (1995) Lipid extracts from membranes of Acholeplasma laidlawii A grown with different fatty acids have a nearly constant spontaneous curvature. Biochim Biophys Acta 1257:18-24
Mannock, D A; McElhaney, R N; Harper, P E et al. (1994) Differential scanning calorimetry and X-ray diffraction studies of the thermotropic phase behavior of the diastereomeric di-tetradecyl-beta-D-galactosyl glycerols and their mixture. Biophys J 66:734-40
Lewis, R N; McElhaney, R N; Osterberg, F et al. (1994) Enigmatic thermotropic phase behavior of highly asymmetric mixed-chain phosphatidylcholines that form mixed-interdigitated gel phases. Biophys J 66:207-16
Lewis, R N; McElhaney, R N; Harper, P E et al. (1994) Studies of the thermotropic phase behavior of phosphatidylcholines containing 2-alkyl substituted fatty acyl chains: a new class of phosphatidylcholines forming inverted nonlamellar phases. Biophys J 66:1088-103

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