The barrier function of the stratum corneum (SC) is intimately related to the structure of the lipid matrix, which is composed of ceramides (Cer), cholesterol (Chol), and free fatty acid (FFA). In this study, the all-atom CHARMM36 (C36) force field is used to simulate bilayers of N-palmitoylsphingosine (Cer16), N-lignoceroylsphingosine (Cer24), Chol, and lignoceric acid (LA) as simple models of the SC. Equimolar mixtures of Cer, Chol, and LA are replicated from experiment for comparison and validation of the C36 force field, and the effects of lipid diversity and temperature are studied. The presence of Chol and LA have effects on nearly all membrane properties including surface area per lipid, area compressibility moduli, chain order, Chol tilt, bilayer thickness, interdigitation, hydrogen bonding, and lipid clustering, while temperature has a more moderate effect. In systems containing Cer16, there is a profound difference in interdigitation between pure Cer and mixed systems, while systems containing Cer24 are relatively unaffected. Increasing temperature has the potential to shift hydrogen bonding pairs rather than uniformly decrease bonding, which can lead to greater Cer–Cer bonding at higher temperatures. Comparison with deuterium order parameter experiments demonstrates good agreement, which supports further use of this class of lipids and fatty acids for development of more complex SC models.

中文翻译：

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纯神经酰胺和三元脂质混合物作为简单内部角质层模型的模拟

角质层（SC）的屏障功能与脂质基质的结构密切相关，脂质基质由神经酰胺（Cer），胆固醇（Chol）和游离脂肪酸（FFA）组成。在这项研究中，全原子CHARMM36（C36）力场用于模拟N-棕榈酰鞘氨醇（Cer16），N的双层-木脂酰鞘氨醇（Cer24），Chol和木质酸（LA）作为SC的简单模型。从实验中复制了Cer，Chol和LA的等摩尔混合物，以比较和验证C36力场，并研究了脂质多样性和温度的影响。Chol和LA的存在对几乎所有膜特性都有影响，包括每个脂质的表面积，面积压缩模量，链序，Chol倾斜度，双层厚度，叉指，氢键和脂质聚集，而温度的影响则更为中等。在包含Cer16的系统中，纯Cer和混合系统之间的交叉指代存在很大差异，而包含Cer24的系统则相对不受影响。温度升高可能会改变氢键对，而不是均匀降低键合，在较高的温度下，这可能导致更大的Cer-Cer键合。与氘序参数实验的比较证明了很好的一致性，这支持进一步使用此类脂质和脂肪酸来开发更复杂的SC模型。