Molecular-level organization of saturated and polyunsaturated fatty acids in a phosphatidylcholine bilayer containing cholesterol.

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TitleMolecular-level organization of saturated and polyunsaturated fatty acids in a phosphatidylcholine bilayer containing cholesterol.
Publication TypeJournal Article
Year of Publication2004
AuthorsPitman, MC, Suits, F, Mackerell, AD, Feller, SE
JournalBiochemistry
Volume43
Issue49
Pagination15318-28
Date Published2004 Dec 14
ISSN0006-2960
KeywordsCholesterol, Computer Simulation, Fatty Acids, Fatty Acids, Unsaturated, Lipid Bilayers, Membrane Microdomains, Models, Chemical, Models, Molecular, Nuclear Magnetic Resonance, Biomolecular, Phosphatidylcholines, Protein Structure, Tertiary, Software, Thermodynamics
Abstract

Cholesterol's preference for specific fatty acid chains is investigated at the atomic level in a 20 ns molecular dynamics computer simulation of a lipid bilayer membrane consisting of cholesterol and 1-stearoyl-2-docosahexaenoyl-sn-glycero-3-phosphocholine (SDPC) in a 1:3 ratio. These simulations reproduce experimental measurements suggesting that cholesterol prefers to be solvated by saturated acyl chains and has a low affinity for polyunsaturated fatty acids. Analyses of the simulation trajectory provide a detailed picture of both the transverse and lateral structures of the lipid bilayer membrane, along with a description of lipid and cholesterol dynamics at high temporal resolution. Comparison with a previous simulation of a pure phospholipid bilayer allows an atomic-level description of the changes in membrane structure and dynamics resulting from incorporation of cholesterol. The observed differential cholesterol interactions with saturated and polyunsaturated lipids provide a mechanism for the formation of laterally inhomogeneous membranes; thus, the simulation provides molecular-level insight into the formation of lipid rafts.

DOI10.1021/bi048231w
Alternate JournalBiochemistry
PubMed ID15581344
Grant ListGM515001 / GM / NIGMS NIH HHS / United States
MCB-0091508 / CB / NCI NIH HHS / United States