PDF(Pubmed)
Abstract：
Skin\'s effectiveness as a barrier to permeation of water and other chemicals rests almost entirely in the outermost layer of the epidermis, the stratum corneum (SC), which consists of layers of corneocytes surrounded by highly organized lipid lamellae. As the only continuous path through the SC, transdermal permeation necessarily involves diffusion through these lipid layers. The role of the SC as a protective barrier is supported by its exceptional lipid composition consisting of ceramides (CERs), cholesterol (CHOL), and free fatty acids (FFAs) and the complete absence of phospholipids, which are present in most biological membranes. Molecular simulation, which provides molecular level detail of lipid configurations that can be connected with barrier function, has become a popular tool for studying SC lipid systems. We review this ever-increasing body of literature with the goals of (1) enabling the experimental skin community to understand, interpret and use the information generated from the simulations, (2) providing simulation experts with a solid background in the chemistry of SC lipids including the composition, structure and organization, and barrier function, and (3) presenting a state of the art picture of the field of SC lipid simulations, highlighting the difficulties and best practices for studying these systems, to encourage the generation of robust reproducible studies in the future. This review describes molecular simulation methodology and then critically examines results derived from simulations using atomistic and then coarse-grained models.
摘要：
皮肤作为水和其他化学物质渗透屏障的有效性几乎完全存在于表皮的最外层，角质层（SC），由高度组织化的脂质层包围的角质细胞层组成。作为通过SC的唯一连续路径，透皮渗透必然涉及通过这些脂质层的扩散。SC作为保护屏障的作用由其由神经酰胺（CERs）组成的特殊脂质组合物支持，胆固醇（CHOL），和游离脂肪酸（FFA）和完全不存在磷脂，存在于大多数生物膜中。分子模拟,它提供了可以与屏障功能相关的脂质构型的分子水平细节，已成为研究SC脂质系统的流行工具。我们回顾了这一不断增加的文献，其目标是（1）使实验皮肤社区能够理解，解释和使用模拟产生的信息，（2）为模拟专家提供SC脂质化学的扎实背景，包括组合物，结构和组织，和屏障功能，和（3）呈现SC脂质模拟领域的最先进的图片，强调研究这些系统的困难和最佳做法，以鼓励未来产生强大的可重复研究。这篇综述描述了分子模拟方法，然后严格检查了使用原子模型和粗粒度模型进行模拟得出的结果。
