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

Abstract

A molecular dynamics (MD) simulation of a fully hydrated, liquid-crystalline dimyristoylphosphatidylcholine (DMPC)-Chol bilayer membrane containing approximately 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 ( approximately 34%), via the hydroxyl oxygen atom (Och); 2) water bridged to carbonyl ( approximately 19%) and nonester phosphate ( approximately 14%) oxygen atoms, via both Och and the hydroxyl hydrogen atom (Hch); and 3) directly hydrogen (H) bonded to carbonyl ( approximately 11%) and nonester phosphate ( approximately 5%) oxygen atoms, via Hch ( approximately 17% of DMPC-Chol links are multiple). DMPC's gamma-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.

Molecular Dynamics Simulations of Ternary Membrane Mixture: Phosphatidylcholine, Phosphatidic Acid, and Cholesterol

“…4E, interact via Columbic interaction between negative charged phosphate group of POPA and positive charged nitrogen atom (N) of choline moiety of POPC. The lipid pairs formed through Columbic interaction were also observed in other lipid simulation systems previously 38,39 . Fig.…”

Molecular Dynamics Simulations of Mixed Micelles Modeling Human Bile

“…The configuration of cholesterol displayed in Figure 7 is typical, with the steroid body inserted radially into the micelle and the hydroxyl group in the interfacial region hydrogen bonded with a phospholipid carbonyl oxygen. The packing of cholesterol is similar to its packing within phospholipid bilayers, as assessed by a number of recent MD simulations (e.g., refs [35][36][37][38]. Although mostly solvated as individual molecules, cholesterol molecules appear to form pairs as well, around 35% of the time.…”

Cholesterol effects on the phospholipid condensation and packing in the bilayer: a molecular simulation study

“…Details concerning the membrane equilibration and validation are described elsewhere [11,12]. The bilayer was simulated for 15 ns using AMBER 4.0 [19].…”

“…The procedure for supplementing the original OPLS base with the missing parameters is described in [21] for DMPC and in [11] for Chol. Atomic charges for DMPC and Chol are given in these papers.…”