Koivuniemi Artturi, Heikelä Mikko, Kovanen Petri T, Vattulainen Ilpo, Hyvönen Marja T
Department of Physics, Tampere University of Technology, Tampere, Finland.
Biophys J. 2009 May 20;96(10):4099-108. doi: 10.1016/j.bpj.2009.01.058.
Cholesteryl esters (CEs) are the water-insoluble transport and storage form of cholesterol. For both transport and storage, phospholipids and proteins embrace the CEs to form an amphipathic monolayer that surrounds the CEs. CEs are transported extracellularly in lipoproteins and are stored intracellularly as cytoplasmic lipid droplets. To clarify the molecular phenomena related to the above structures, we conducted atomistic molecular-dynamics simulations for a spherical, approximately high density lipoprotein sized lipid droplet comprised of palmitoyl-oleoyl-phosphatidylcholine (POPC) and cholesteryl oleate (CO) molecules. An additional simulation was conducted for a lamellar lipid trilayer consisting of the same lipid constituents. The density profiles showed that COs were located in the core of the spherical droplet. In trilayer simulations, CO molecules were also in the core and formed two denser strata. This is remarkable because the intra- and intermolecular behaviors of the COs were similar to previous findings from bulk COs in the fluid phase. In accordance with previous experimental studies, the solubility of COs in the POPC monolayers was found to be low. The orientation distribution of the sterol moiety with respect to the normal of the system was found to be broad, with mainly isotropic or slightly parallel orientations observed deep in the core of the lipid droplet or the trilayer, respectively. In both systems, the orientation of the sterol moiety changed to perpendicular with respect to the normal close to the phopsholipid monolayers. Of interest, within the POPC monolayers, the intramolecular conformation of the COs varied from the previously proposed horseshoe-like conformation to a more extended one. From a metabolic point of view, the observed solubilization of CEs into the phospholipid monolayers, and the conformation of CEs in the phospholipid monolayers are likely to be important regulatory factors of CE transport and hydrolysis.
胆固醇酯（CEs）是胆固醇的水不溶性运输和储存形式。为了实现运输和储存，磷脂和蛋白质包裹着CEs，形成围绕CEs的两亲性单层。CEs在脂蛋白中进行细胞外运输，并作为细胞质脂滴在细胞内储存。为了阐明与上述结构相关的分子现象，我们对由棕榈酰油酰磷脂酰胆碱（POPC）和油酸胆固醇酯（CO）分子组成的球形、近似高密度脂蛋白大小的脂滴进行了原子分子动力学模拟。还对由相同脂质成分组成的层状脂质三层膜进行了额外的模拟。密度分布表明，COs位于球形脂滴的核心。在三层膜模拟中，CO分子也位于核心并形成两个密度更高的层。这很显著，因为COs的分子内和分子间行为与先前在流体相中大量COs的研究结果相似。根据先前的实验研究，发现COs在POPC单层中的溶解度较低。发现甾醇部分相对于系统法线的取向分布很宽，在脂滴或三层膜的核心深处分别主要观察到各向同性或略平行的取向。在这两个系统中，甾醇部分的取向在靠近磷脂单层处变为垂直于法线。有趣的是，在POPC单层内，COs的分子内构象从先前提出的马蹄形构象变为更伸展的构象。从代谢的角度来看，观察到的CEs溶解到磷脂单层中以及CEs在磷脂单层中的构象可能是CE运输和水解的重要调节因素。
