Structural Changes in Ceramide Bilayers Rationalize Increased Permeation through Stratum Corneum Models with Shorter Acyl Tails

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• 作者：Mark茅ta Palonc媒ov谩 ; Kate艡ina V谩vrov谩 ; 沤ofie Sovov谩 ; Russell DeVane ; Michal Otyepka ; Karel Berka
• 刊名：Journal of Physical Chemistry B
• 出版年：2015
• 出版时间：July 30, 2015
• 年：2015
• 卷：119
• 期：30
• 页码：9811-9819
• 全文大小：564K
• ISSN：1520-5207

文摘

Ceramides are indispensable constituents of the stratum corneum (SC), the uppermost impermeable layer of human skin. Ceramides with shorter (four- to eight-carbon acyl chains) fatty acid chains increase skin and model membrane permeability, while further shortening of the chain leads to increased resistance to penetration almost as good as that of ceramides from healthy skin (24 carbons long on average). Here we address the extent to which the atomistic CHARMM36 and coarse-grain MARTINI molecular dynamics (MD) simulations reflect the skin permeability data. As a result, we observed the same bell-shaped permeability trend for water that was observed in the skin and multilayer membrane experiments for model compounds. We showed that the enhanced permeability of the short ceramides is mainly caused by the disturbance of their headgroup conformation because of their inability to accommodate the shorter lipid acyl chain into a typical hairpin conformation, which further led to their destabilization and phase separation. As MD simulations described well delicate structural features of SC membranes, they seem to be suitable for further studies of the SC superstructure, including the development of skin penetration enhancers for transdermal drug delivery and skin toxicity risk assessment studies.