1 Department of Physics, Chemistry and Pharmacy, Faculty of Science, SDU2 SDU eScience Centre, Department of Mathematics and Computer Science (IMADA), Faculty of Science, SDU3 Department of Physics, Chemistry and Pharmacy, Faculty of Science, SDU
Cholesteryl esters (CEs) are a form of cholesterol (CHOL) storage in the living cells, as opposed to free CHOL. CEs are major constituents of low density lipoprotein particles. Therefore, CEs are implicated in provoking atherosclerosis. Arranged into cytoplasmic lipid droplets (LDs), CEs are stored intracellularly. They can also be transported extracellularly by means of lipoproteins. In this work, large-scale molecular dynamics (MD) simulations are used to characterize the molecular structure of LDs containing various fractions (10-50 mol %) of cholesteryl oleate (CO) with respect to triolein (TO) fraction. The simulated LDs were covered by a phospholipid monolayer formed by a mixture of 1-palmitoyl-2-oleoylphosphatidylcholine, POPC (75 mol %), and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine, POPE (25 mol %), molecules. We report that most CO molecules are located within the hydrophobic core of LDs, whereas a small fraction (0.3-1.9 mol %) penetrates the monolayer. The solubility of CO in the phospholipid monolayer is relatively small. Due to a good miscibility with TO molecules, CO forms a liquid phase inside LD at 333 K. There is long-range order in the liquid TO-CO droplet core up to 8 nm from the phospholipid interface, resulting from the structuring of hydrophilic groups. This structuring slowly decays in the direction toward the LD center of mass. No sorting of TO and CO is detected, irrespective of the molar fractions simulated. The distribution of CO within the LDs is significant in determining the rate of their hydrolysis by surface-bound enzyme lipases, and thus has a subsequent impact on the levels of CO in plasma and LDLs.
Journal of Physical Chemistry Part B: Condensed Matter, Materials, Surfaces, Interfaces and Biophysical, 2014, Vol 118, Issue 38, p. 11145-51