The molecular arrangement of ceramides in the unit cell of the long periodicity phase of stratum corneum models shows a high adaptability to different ceramide head group structures

The stratum corneum (SC) lipid matrix, composed primarily of ceramides (CERs), cholesterol and free fatty acids (FFA), has an important role for the skin barrier function. The presence of the long periodicity phase (LPP), a unique lamellar phase, is characteristic for the SC. Insight into the lipid molecular arrangement within the LPP unit cell is imperative for understanding the relationship between the lipid subclasses and the skin barrier function. In this study, the impact of the CER head group structure on the lipid arrangement and barrier functionality was investigated using lipid models forming the LPP. The results demonstrate that the positions of CER N-(tetracosanoyl)-sphingosine (CER NS) and CER N-(tetracosanoyl)-phytosphingosine (CER NP), two essentials CER subclasses, are not influenced by the addition of another CER subclass (N-(tetracosanoyl)-dihydrosphingosine (CER NdS), N-(2R-hydroxy-tetracosanoyl)-sphingosine (CER AS) or D-(2R-hydroxy-tetracosanoyl)-phytosphingosine (CER AP)). However, differences are observed in the lipid organization and the hydrogen bonding network of the three different models. A similar localization of CER NP and CER NS is also observed in a more complex lipid model, with the CER subclass composition mimicking that of human SC. These studies show the adaptability and insensitivity of the LPP unit cell structure to changes in the lipid head group structures of the CER subclasses.