Department of Physics, University of South Florida, Tampa, Florida 33620, United States.
J Phys Chem B. 2012 Apr 19;116(15):4500-9. doi: 10.1021/jp212325e. Epub 2012 Apr 6.
Ceramide is the simplest molecule in the class of glycosphingolipids composed of a sphingosine backbone and acyl moiety. It plays significant roles in cell signaling; apoptosis; binding of hormones, toxins, and viruses; and many other biologically important functions. Sphingomyelin, ceramide with a phosphotidylcholine headgroup, is another biologically vital lipid present in the myelin sheath of nerve cell axons. Regions with high concentrations of ceramide can be formed in biological membranes composed of sphingomyelin by enzymatic catalysis with sphingomyelinase. To better understand the biophysical and thermodynamic properties of these molecules and their mixtures, we have preformed NPT molecular dynamics simulations of hydrated 16:0 sphingomyelin bilayers with increasing concentrations of 16:0 ceramide at 323, 332, 340, and 358 K. From analyses of electron densities, hydrogen bonding, NMR order parameters, partial molecular volume, and partial molecular area, we have identified possible structural changes corresponding to liquid ordered and liquid disordered phases. These structural changes are the results of changes in intra- and intermolecular hydrogen bonds between SM and Cer molecules. Our results correspond to DSC experiments for sphingomyelin bilayer concentrations up to 50% Cer. Above 50% concentration, we observe conformational changes in the SM headgroup similar to that of the umbrella model for lipid cholesterol mixtures.
神经酰胺是糖鞘脂类中最简单的分子，由神经酰胺骨架和酰基部分组成。它在细胞信号转导、细胞凋亡、激素、毒素和病毒结合以及许多其他重要的生物学功能中发挥重要作用。神经鞘磷脂是神经细胞轴突髓鞘中另一种重要的生物脂质，是一种带有磷酸胆碱头基的神经酰胺。通过鞘磷脂酶的酶促催化，可以在由鞘磷脂组成的生物膜中形成具有高浓度神经酰胺的区域。为了更好地了解这些分子及其混合物的生物物理和热力学性质，我们在 323、332、340 和 358 K 下对含有 16:0 神经酰胺的水合 16:0 神经鞘磷脂双层进行了 NPT 分子动力学模拟，浓度逐渐增加。通过分析电子密度、氢键、NMR 序参数、部分分子体积和部分分子面积，我们确定了与液体有序相和液体无序相相对应的可能结构变化。这些结构变化是 SM 和 Cer 分子之间的分子内和分子间氢键变化的结果。我们的结果与 DSC 实验相对应，实验对象是浓度高达 50% Cer 的神经鞘磷脂双层。在 50%以上的浓度下，我们观察到 SM 头部基团的构象变化，类似于脂质胆固醇混合物的伞模型。
