Web Release Date: November 12,
Molecular-Level Organization of Saturated and Polyunsaturated Fatty Acids in a
Phosphatidylcholine Bilayer Containing Cholesterol
IBM T. J. Watson Research Center, Yorktown Heights, New York 10598
Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland, Baltimore, Maryland 21201
Department of Chemistry, Wabash College, Crawfordsville, Indiana 47933
Received August 16, 2004
Revised Manuscript Received September 27, 2004
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.
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