Zhang Zhancheng, Lu Lanyuan, Berkowitz Max L
Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
J Phys Chem B. 2008 Mar 27;112(12):3807-11. doi: 10.1021/jp077735b. Epub 2008 Feb 29.
It is believed that natural biological membranes contain domains of lipid ordered phase enriched in cholesterol and sphingomyelin. Although the existence of these domains, called lipid rafts, is still not firmly established for natural membranes, direct microscopic observations and phase diagrams obtained from the study of three-component mixtures containing saturated phospholipids, unsaturated phospholipids, and cholesterol demonstrate the existence of lipid rafts in synthetic membranes. The presence of the domains or rafts in these membranes is often ascribed to the preferential interactions between cholesterol and saturated phospholipids, for example, between cholesterol and sphingomyelin. In this work, we calculate, using molecular dynamics computer simulation technique, the free energy of cholesterol transfer from the bilayer containing unsaturated phosphatidylcholine lipid molecules to the bilayer containing sphingomyelin molecules and find that the affinity of cholesterol to sphingomyelin is higher. Our calculations of the free-energy components, energy and entropy, show that cholesterol transfer is exothermic and promoted by the favorable change in the lipid-lipid interactions near cholesterol and not by the favorable energy of cholesterol-sphingomyelin interaction, as assumed previously.
据信，天然生物膜含有富含胆固醇和鞘磷脂的脂质有序相结构域。尽管对于天然膜而言，这些被称为脂筏的结构域的存在尚未得到确凿证实，但通过对包含饱和磷脂、不饱和磷脂和胆固醇的三元混合物的研究获得的直接显微镜观察结果和相图表明，合成膜中存在脂筏。这些膜中结构域或脂筏的存在通常归因于胆固醇与饱和磷脂之间的优先相互作用，例如胆固醇与鞘磷脂之间的相互作用。在这项工作中，我们使用分子动力学计算机模拟技术计算了胆固醇从不饱和磷脂酰胆碱脂质分子双层转移到鞘磷脂分子双层的自由能，发现胆固醇对鞘磷脂的亲和力更高。我们对自由能成分、能量和熵的计算表明，胆固醇转移是放热的，并且是由胆固醇附近脂质 - 脂质相互作用的有利变化促进的，而不是像之前假设的那样由胆固醇 - 鞘磷脂相互作用的有利能量促进的。
