Atomistic Simulation Studies of Cholesteryl Oleates: Model for the Core of Lipoprotein Particles

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 2x10(-9) cm2/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.

Lipid Simulations: A Perspective on Lipids in Action

“…For example, the properties of the lipoprotein core have been studied both for cholesteryl esters and triglycerides (Heikelä et al 2006;Hall et al 2008). HDL discs have also been paid considerable attention (Shih et al 2005(Shih et al , 2008Catte et al 2006), and recent work on spheroidal HDL has been very illuminating (Catte et al 2008;Koivuniemi et al 2009).…”

Modeling order-disorder transition in Low-Density Lipoprotein

“…These motions are accompanied with some degree of bond isomerism. Motions are suppressed in double bond region of the chain, but after that, they again become strong and increase toward the end of the chain [9]. Thus we conclude that the final orderdisorder melting process is driven by liberated motion of acyl chains in a liquid state, and increased disorder possibly due to some degree of the bond isomerism.…”

Calculation of the T‐X Phase Diagrams for Binary Mixtures of Cholestanyl Myristate–Cholesteryl Myristate and Cholestanyl Myristate–Cholesteryl Oleate

“…For a binary mixture of CnM-CrM, we obtained the phase line equations, Eqs. (7), (12), (16), and (22), respectively, for the transitions of the isotropic liquid-cholesteric, cholesteric-smectic, smectic-isotropic liquid, and isotropic liquid-solid solution. These equations were then fitted to the experimental data for the binary phase map of the CnM-CrM system obtained by DSC and microscopy.…”

“…Recently, crystallization behavior of the smectic phase of this liquid crystal 21 has been investigated. For cholesteryl oleate (CO), a system of 128 molecules was constructed by simulation to investigate its structural and dynamical properties 22 …”

“…For cholesteryl oleate (CO), a system of 128 molecules was constructed by simulation to investigate its structural and dynamical properties. 22 Binary mixtures of CrM have also been studied experimentally. For a mixture of cholesteryl chloride and CrM, the transition between the β-cholesteric phase at low temperatures and the α-cholesteric phase at high temperatures has been studied thermodynamically.…”