NMR experiments were performed to study the influence of the degree of fatty acid unsaturation and headgroup composition on (i) lipid-lipid interaction, (ii) peptide-lipid interaction, and (iii) alcohol-lipid interaction. (i) Lipid-lipid interaction. The influence of polyunsaturation on the conformation and motional properties of phosphatidylcholine bilayers is being studied. The investigation of the phase diagram of (18:0) (22:6) PE is in progress. Changes in the average order of hydrocarbon methylene segments are interpreted as a change in the hydrophobic thickness of the bilayer. The lamellar-hexagonal phase transition temperature is used to quantitate membrane stress acting on proteins incorporated into bilayers of polyunsaturated lipids. (ii) Peptide-lipid interaction. Secondary peptide structure, lipid organization, and the strength of peptide-lipid interaction are strongly correlated. The amphipathic peptide P828 changes its secondary structure upon interaction with negatively charged DOPG and causes formation of DOPG domains in DOPG/DOPC mixtures. Experiments with tannic acid show that high concentration of hydroxyl groups at molecular surfaces facilitate the interaction of molecules with the lipid water interface. NMR methods have been developed to verify the transmembrane orientation of a hydrophobic helical peptide. A small amount of the peptide alamethicin in DEPE or DOPE/DOPC (3/1) membranes converts the lamellar lipid phase into a cubic phase. (iii) Alcohol lipid interaction. The interaction of ethanol with phosphatidylcholine, and phosphatidylethanolamine is being studied. Partially hydrated membranes interact strongly with ethanol. The amount of bound ethanol decreases with increasing water/lipid ratios. We speculate that the strength of ethanol-lipid interaction is related to water activity.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Intramural Research (Z01)
Project #
1Z01AA000003-02
Application #
3745190
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
1994
Total Cost
Indirect Cost
Name
National Institute on Alcohol Abuse and Alcoholism
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Teague Jr, Walter E; Soubias, Olivier; Petrache, Horia et al. (2013) Elastic properties of polyunsaturated phosphatidylethanolamines influence rhodopsin function. Faraday Discuss 161:383-95; discussion 419-59
Gawrisch, Klaus (2012) Tafazzin senses curvature. Nat Chem Biol 8:811-2
Kimura, Tomohiro; Cheng, Kejun; Rice, Kenner C et al. (2009) Location, structure, and dynamics of the synthetic cannabinoid ligand CP-55,940 in lipid bilayers. Biophys J 96:4916-24
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Gawrisch, Klaus; Soubias, Olivier (2008) Structure and dynamics of polyunsaturated hydrocarbon chains in lipid bilayers-significance for GPCR function. Chem Phys Lipids 153:64-75
Gawrisch, Klaus; Gaede, Holly C (2007) Measurement of lateral diffusion rates in membranes by pulsed magnetic field gradient, magic angle spinning-proton nuclear magnetic resonance. Methods Mol Biol 400:257-65
Veatch, Sarah L; Soubias, Olivier; Keller, Sarah L et al. (2007) Critical fluctuations in domain-forming lipid mixtures. Proc Natl Acad Sci U S A 104:17650-5

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