The Role of 1-O-Acylceramide NP in Structural Organization and Permeability of the Stratum Corneum Lipid Matrix

ABSTRACT The extracellular lipid matrix in the stratum corneum (SC) is crucial for generating a skin barrier (permeability) function. The lipid matrix contains three major components; ceramides, cholesterol, and free fatty acids. The broad diversity of ceramides depends on their molecular structures ( e.g ., hydroxylations and chain lengths) and plays a critical role in maintaining the structural integrity of the lipid matrix. Although recent studies identified a new subclass of ceramide, 1- O -acylceramide NP (CerENP), its precise role in the lipid matrix of SC is still elusive. Herein, we investigate the role of CerENP on the structure and permeability of the SC by molecular dynamics simulations. Our results suggest that the CerENP molecules induce a denser lipid matrix in the lateral dimension in the long periodicity phase model with a bilayer-slab- bilayer structure. Moreover, ethanol permeability analysis indicates that CerENP can suppress molecular permeability through the lipid matrix. This study provides insight into the role of a new subclass of ceramide in the SC, which can lead to our better understanding of skin organization and disease-related barrier dysfunction.