A MODEL MEMBRANE APPROACH TO THE EPIDERMAL PERMEABILITY BARRIER

The permeability barrier of mammalian skin is found in unusual intercellular domains in the upper layers of the epidermis, and is composed mainly of three lipid classes: ceramide, cholesterol, and free fatty acid. These are organized as lamellae, but the details of lipid organization are nor precisely known. To examine the relationship between lipid composition and phase behavior, aqueous dispersions of bovine brain ceramide, cholesterol, and perdeuterated palmitic acid were examined by H-2 NMR and compared to analogous systems in which sphingomyelin replaced ceramide. The sphingomyelin systems give rise as expected to a stable fluid lamellar signal over the temperature range 20-75 degrees C and pH 5.2-7.4, whereas the ceramide dispersions show complex polymorphism as a function of both temperature and pH. Prominent features of the ceramide dispersions containing cholesterol are phase coexistence and the presence of a ''solid'' phase in which molecular motion is more inhibited than in a classical phospholipid gel phase: T-1z measurements indicate that lateral diffusion of the palmitic acid probe effectively does not occur. In the absence of cholesterol, a fluid lamellar signal is not observed, but the appearance of a ''solid'' signal is also influenced by the pH. In the presence of cholesterol, a fluid lamellar signal is present at 50 degrees C, and the H-2 NMR order parameter profile is very similar to that derived from the analogous sphingomyelin dispersions. We interpret these results as evidence that the lipid composition of stratum corneum intercellular membranes will confer physical properties that are considerably different from those of the vast majority of mammalian cell membranes, and speculate that such organization is critical to physiological function.