Biophys J, March 2000, p. 1376-1389, Vol. 78, No. 3

Cholesterol Effects on the Phosphatidylcholine Bilayer Polar Region: A Molecular Simulation Study

Marta Pasenkiewicz-Gierula,^* Tomasz Róg,^* Kunihiro Kitamura, and Akihiro Kusumi^§

 ^*Department of Biophysics, Institute of Molecular Biology, Jagiellonian University, Kraków, Poland;  Department of Molecular Science, Research Center, Taisho Pharmaceutical Co., Saitama 330, Japan;  Department of Biological Science, Graduate School of Science, Nagoya University, Nagoya 464-8602, Japan; and  ^§Kusumi Membrane Organizer Project, ERATO, Japan Science and Technology Corporation, Nagoya 460-0012, Japan

A molecular dynamics (MD) simulation of a fully hydrated, liquid-crystalline dimyristoylphosphatidylcholine (DMPC)-Chol bilayer membrane containing ~22 mol% Chol was carried out for 4.3 ns. The bilayer reached thermal equilibrium after 2.3 ns of MD simulation. A 2.0-ns trajectory generated during 2.3-4.3 ns of MD simulation was used for analyses to determine the effects of Chol on the membrane/water interfacial region. In this region, 70% of Chol molecules are linked to DMPC molecules via short-distance interactions, where the Chol hydroxyl group (OH-Chol) is 1) charge paired to methyl groups of the DMPC choline moiety (~34%), via the hydroxyl oxygen atom (Och); 2) water bridged to carbonyl (~19%) and nonester phosphate (~14%) oxygen atoms, via both Och and the hydroxyl hydrogen atom (Hch); and 3) directly hydrogen (H) bonded to carbonyl (~11%) and nonester phosphate (~5%) oxygen atoms, via Hch (~17% of DMPC-Chol links are multiple). DMPC's -chain carbonyl oxygen atom is involved in 44% of water bridges and 51% of direct H bonds formed between DMPC and Chol. On average, a Chol molecule forms 0.9 links with DMPC molecules, while a DMPC molecule forms 2.2 and 0.3 links with DMPC and Chol molecules, respectively. OH-Chol makes hydrogen bonds with 1.1 water molecules, preferentially via Hch. The average number of water molecules H bonded to the DMPC headgroup is increased by 7% in the presence of Chol. These results indicate that inclusion of Chol decreases interlipid links and increases hydration in the polar region of the membrane.

Biophys J, March 2000, p. 1376-1389, Vol. 78, No. 3
© 2000 by the Biophysical Society   0006-3495/00/03/1376/14  $2.00

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