A MODEL MEMBRANE APPROACH TO THE EPIDERMAL PERMEABILITY BARRIER

The permeability barrier of mammalian skin is found in unusual interce llular domains in the upper layers of the epidermis, and is composed m ainly of three lipid classes: ceramide, cholesterol, and free fatty ac id. These are organized as lamellae, but the details of lipid organiza tion are nor precisely known. To examine the relationship between lipi d composition and phase behavior, aqueous dispersions of bovine brain ceramide, cholesterol, and perdeuterated palmitic acid were examined b y H-2 NMR and compared to analogous systems in which sphingomyelin rep laced ceramide. The sphingomyelin systems give rise as expected to a s table fluid lamellar signal over the temperature range 20-75 degrees C and pH 5.2-7.4, whereas the ceramide dispersions show complex polymor phism 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 mor e inhibited than in a classical phospholipid gel phase: T-1z measureme nts indicate that lateral diffusion of the palmitic acid probe effecti vely does not occur. In the absence of cholesterol, a fluid lamellar s ignal is not observed, but the appearance of a ''solid'' signal is als o influenced by the pH. In the presence of cholesterol, a fluid lamell ar signal is present at 50 degrees C, and the H-2 NMR order parameter profile is very similar to that derived from the analogous sphingomyel in dispersions. We interpret these results as evidence that the lipid composition of stratum corneum intercellular membranes will confer phy sical properties that are considerably different from those of the vas t majority of mammalian cell membranes, and speculate that such organi zation is critical to physiological function.