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ABSTRACT
We have conducted molecular dynamics simulations to gain insight into the atomic-scale properties of an isotropic system of cholesteryl oleate (CO) molecules. Cholesteryl esters are major constituents of low density lipoprotein particles, the key players in the formation of atherosclerosis, as well as the storage form of cholesterol. Here the aim is to clarify structural and dynamical properties of CO molecules under conditions, which are suggestive of those in the core of low density lipoprotein particles. The simulations in the fluid phase indicate that the system of CO molecules is characterized by an absence of translational order, as expected, while the orientational order between distinct CO molecules is significant at short distances, persisting over a molecular size. As for intramolecular properties, the bonds along the oleate chain are observed to be weakly ordered with respect to the sterol structure, unlike the bonds along the short hydrocarbon chain of cholesterol where the ordering is significant. The orientational distribution of the oleate chain as a whole with respect to the sterol moiety is of broad nature, having a major amount of extended and a less considerable proportion of bended structures. Distinct transient peaks at specific angles also appear. The diffusion of CO molecules is found to be a slow process and characterized by a diffusion coefficient of the order of 2 × 10^sup -9^ cm^sup 2^/s. This is considerably slower than diffusion, e.g., in ordered domains of lipid membranes rich in sphingomyelin and cholesterol. Analysis of the rotational diffusion rates and trans-to-gauche transition rates yield results consistent with experiments.
INTRODUCTION
Cholesteryl esters (CEs) are lengthy molecules where a long fatty acyl chain is attached to the OH group of cholesterol. Practically, cholesteryl ester is the extracellular transport and intracellular storage form of cholesterol, containing mainly linoleate and oleate fatty acids in these functions, respectively (1). In the intravascular transport, cholesteryl esters are formed with the help of lecithin-cholesterol acyl transterase enzyme to carry cholesterol in a more hydrophobic form in the nonaqueous interior of lipoprotein particles, mostly low density lipoprotein (LDL) entities. LDL particles are known as key players in the formation of atherosclerotic lesions in the arterial intima because of the propensity of their modified forms to accumulate extracellularly in the form of small...