Cholesterol shows preference for the interior of polyunsaturated lipid membranes.
Recent neutron scattering experiments showed a striking manifestation of the aversion between polyunsaturated fatty acid (PUFA)-containing lipids and cholesterol. Selectively deuterated cholesterol/ 1,2-diarachidonylphosphatidylcholine (DAPC) samples revealed that the hydroxyl of the sterol resides at the center of the bilayer. Here we use a recently parametrized coarse grain simulation model to shed light on these puzzling experimental observations. Using a simulation setup in close correspondence to the experimental conditions, we reproduce the experimental neutron scattering profiles to a large extent. The simulations allow us to analyze the behavior of cholesterol in detail; we show that the interaction of cholesterol with the PUFA chains of DAPC leads to a fast flip-flop rate for the sterol and an increased preference of the sterol for the unusual location embedded between the monolayer leaflets.
Marrink
Siewert J
SJ
Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Nijenborgh 4, 9747 AG Groningen, The Netherlands. s.j.marrink@rug.nl
de Vries
Alex H
AH
Harroun
Thad A
TA
Katsaras
John
J
Wassall
Stephen R
SR
D001665:Binding Sites; D002784:Cholesterol / Q000737:chemistry / Q000378:metabolism*; D005231:Fatty Acids, Unsaturated / Q000737:chemistry / Q000378:metabolism*; D008051:Lipid Bilayers / Q000737:chemistry / Q000378:metabolism*; D033363:Neutron Diffraction; D010713:Phosphatidylcholines
D005231:Fatty Acids, Unsaturated; D008051:Lipid Bilayers; D010713:Phosphatidylcholines; C044819:1,2-diarachidonoyl-glycero-3-phosphocholine; D002784:Cholesterol