Molecular-level organization of saturated and polyunsaturated fatty acids in a phosphatidylcholine bilayer containing cholesterol.
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.
Pitman
Michael C
MC
IBM T. J. Watson Research Center, Yorktown Heights, New York 10598, USA.
Suits
Frank
F
Mackerell
Alexander D
AD
Feller
Scott E
SE
D002784:Cholesterol / Q000737:chemistry*; D003198:Computer Simulation; D005227:Fatty Acids / Q000737:chemistry*; D005231:Fatty Acids, Unsaturated / Q000737:chemistry*; D008051:Lipid Bilayers / Q000737:chemistry*; D021962:Membrane Microdomains / Q000737:chemistry; D008956:Models, Chemical; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D010713:Phosphatidylcholines / Q000737:chemistry*; D017434:Protein Structure, Tertiary; D012984:Software; D013816:Thermodynamics
D005227:Fatty Acids; D005231:Fatty Acids, Unsaturated; D008051:Lipid Bilayers; D010713:Phosphatidylcholines; D002784:Cholesterol