Structure and dynamics of cholesterol-containing polyunsaturated lipid membranes studied by neutron diffraction and NMR.

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TitleStructure and dynamics of cholesterol-containing polyunsaturated lipid membranes studied by neutron diffraction and NMR.
Publication TypeJournal Article
Year of Publication2011
AuthorsMihailescu, M, Soubias, O, Worcester, D, White, SH, Gawrisch, K
JournalJ Membr Biol
Volume239
Issue1-2
Pagination63-71
Date Published2011 Jan
ISSN1432-1424
KeywordsCell Membrane, Cholesterol, Docosahexaenoic Acids, Lipid Bilayers, Membrane Lipids, Neutron Diffraction, Nuclear Magnetic Resonance, Biomolecular, Phosphatidylcholines, Thermodynamics
Abstract

A direct and quantitative analysis of the internal structure and dynamics of a polyunsaturated lipid bilayer composed of 1-stearoyl-2-docosahexaenoyl-sn-glycero-3-phosphocholine (18:0-22:6n3-PC) containing 29 mol% cholesterol was carried out by neutron diffraction, (2)H-NMR and (13)C-MAS NMR. Scattering length distribution functions of cholesterol segments as well as of the sn-1 and sn-2 hydrocarbon chains of 18:0-22:6n3-PC were obtained by conducting experiments with specifically deuterated cholesterol and lipids. Cholesterol orients parallel to the phospholipids, with the A-ring near the lipid glycerol and the terminal methyl groups 3 Å away from the bilayer center. Previously, we reported that the density of polyunsaturated docosahexaenoic acid (DHA, 22:6n3) chains was higher near the lipid-water interface. Addition of cholesterol partially redistributes DHA density from near the lipid-water interface to the center of the hydrocarbon region. Cholesterol raises chain-order parameters of both stearic acid and DHA chains. The fractional order increase for stearic acid methylene carbons C(8)-C(18) is larger, reflecting the redistribution of DHA chain density toward the bilayer center. The correlation times of DHA chain isomerization are short and mostly unperturbed by the presence of cholesterol. The uneven distribution of saturated and polyunsaturated chain densities and the cholesterol-induced balancing of chain distributions may have important implications for the function and integrity of membrane receptors, such as rhodopsin.

DOI10.1007/s00232-010-9326-6
Alternate JournalJ. Membr. Biol.
PubMed ID21161517
PubMed Central IDPMC3030944
Grant ListR01 GM074637 / GM / NIGMS NIH HHS / United States