Skin Lipids: Localization of Ceramide and Fatty Acid in the Unit Cell of the Long Periodicity Phase

The lipid matrix of the skin’s stratum corneum plays a key role in the barrier function, which protects the body from desiccation. The lipids that make up this matrix consist of ceramides, cholesterol, and free fatty acids, and can form two coexisting crystalline lamellar phases: the long periodicity phase (LPP) and the short periodicity phase (SPP). To fully understand the skin barrier function, information on the molecular arrangement of the lipids in the unit cell of these lamellar phases is very desirable. To determine this arrangement in previous studies, we examined the molecular arrangement of the SPP. In this study, neutron diffraction studies were performed to obtain information on the molecular arrangement of the LPP. The diffraction pattern reveals nine diffraction orders attributed to the LPP with a repeating unit of 129.4 ± 0.5 Å. Using D2O/H2O contrast variation, the scattering length density profiles were calculated for protiated samples and samples that included either the perdeuterated acyl chain of the most abundant ceramide or the most abundant perdeuterated fatty acid. Both perdeuterated chains are predominantly located in the central part of the unit cell with substantial interdigitation of the acyl chains in the unit cell center. However, a fraction of the perdeuterated chains is also located near the border of the unit cell with their acyl chains directing toward the center. This arrangement of lipids in the LPP unit cell corresponds with the location of their lipid headgroups at the border and also inside of the unit cell at a well-defined position (±21 Å from the unit cell center), indicative of a three-layer lipid arrangement within the 129.4 ± 0.5 Å repeating unit.