Effects of epicholesterol on the phosphatidylcholine bilayer: a molecular simulation study

Abstract

Epicholesterol (Echol) is an epimeric form of cholesterol (Chol). A molecular dynamics simulation of the fully hydrated dimyristoylphosphatidylcholine-Echol (DMPC-Echol) bilayer membrane containing approximately 22 mol % of Echol was carried out for 5 ns. A 3-ns trajectory generated between 2 and 5 ns of molecular dynamics simulation was used for analyses to determine the effects of Echol on the membrane properties. As reference systems, pure DMPC and mixed DMPC-Chol bilayers were used. The study shows that Echol, like Chol, changes the organization of the bilayer/water interface and increases membrane order and condensation, but to a lesser degree. Effects of both sterols are based on the same atomic level mechanisms; their different strength arises from different vertical localizations of Echol and Chol hydroxyl groups in the membrane/water interface.

FIGURE 1

Molecular structures of (a) DMPC, and (b) Chol molecules with numbering of atoms (the chemical symbol for carbon atoms, C, is omitted) and torsion angles. The Chol rings are labeled A, B, C, and D.

FIGURE 2

Three-dimensional structures of (a) Chol, and (b) Echol molecules. The smooth (α-face) and rough (β-face) faces of sterol molecules are labeled.

FIGURE 3

Time profiles of the (a) temperature, (b) potential energy, (c) surface area per DMPC, and (d) number of gauche bonds per chain in DMPC-Echol bilayer. The thin lines in c and d indicate average values after equilibration of, respectively, the surface area of 57.5 Ų/DMPC, and gauche bonds per chain (compare to text), of 2.3 ± 0.1.

FIGURE 4

Profiles of the atom density of Op (dashed line), and sterol HO group (solid line) in DMPC-Chol (black line) and DMPC-Echol (gray line) bilayers.

FIGURE 5

Profiles of the molecular order parameter (S_mol) calculated for the DMPC (a) β-chain, and (b) γ-chain in pure DMPC (•), DMPC-Chol (○), and DMPC-Echol (▵) bilayers.

FIGURE 6

Probabilities of gauche conformations along the (a) β-chain, and (b) γ-chain in pure DMPC (•), DMPC-Chol (○), and DMPC-Echol (▵) bilayers.

FIGURE 7

Profiles of lifetimes of the trans (▪, □, ▿), and gauche (•, ○, ▵) conformations along the (a) β-chain, and (b) γ-chain in pure DMPC (▪, •), DMPC-Chol (□, ○), and DMPC-Echol (▿, ▵) bilayers.

FIGURE 8

Three-dimensional radial distribution functions (RDF) for carbon atoms in the hydrophobic core of pure DMPC (dotted line), DMPC-Chol (solid gray line), and DMPC-Echol (solid black line) bilayers.

FIGURE 9

Profiles of the number of neighbors (NS) (compare to text) along the (a) β-chain, and (b) γ-chain in DMPC (•), DMPC-Chol (○), and DMPC-Echol (▵) bilayers.