ROLE OF CERAMIDE-1 IN THE MOLECULAR-ORGANIZATION OF THE STRATUM-CORNEUM LIPIDS

The main barrier of the skill is formed by the lipids in the apical sk in layer the stratum corneum (SC). In SC mainly ceramides (CER), free fatty acids (FFA) and cholesterol (CHOL) are present. Tile CER are com posed of at least six different fractions. CER 1 has an exceptional mo lecular structure as it contains a linoleic acid linked to a long-chai n omega-hydroxy acid !(C > 30). The SC lipids are organized in two lam ellar phases with periodicities of approximately 6 and 13 nm, respecti vely. Recent studies revealed that ceramides isolated from pig SC mixe d with cholesterol in confined ratios mimic stratum corneum lipid phas e behavior closely (Bouwstra, J.A., ct al. 1996. J. Lif,in Res. 37:999 -1011). In this paper the role of CER 1 for the SC lipid lamellar orga nization was studied. For this purpose lipid phase behavior of mixture s of CHOL and total ceramide fraction was compared with that of mixtur es of CHOL and a ceramide mixture lacking CER 1. These studies showed that in the absence of CER 1 almost no long periodicity phase was form ed over a wide CHOL/CER molar ratio. A model is proposed for the molec ular arrangement of the two lamellar phases. This model is based on th e dominant role CER 1 plays in the formation of the long periodicity p hase, electron density distribution calculations, and observations, su ch as i) the bimodal distribution of the fatty acid chain lengths of t he ceramides, ii) the phase separation between long-chain ceramides an d short-chain ceramides in a monolayer approach, and iii) the absence of swelling of the lamellae upon increasing the water content organiza tion in SC. In this molecular model the short periodicity phase is com posed of only two high electron density regions indicating the presenc e of only one bilayer, similar to that often found in phospholipid mem branes. The molecular arrangement in the long periodicity phase is ver y exceptional. This phase most probably consists of two broad and one narrow low electron density regions. The two broad regions are formed by partly interdigitating ceramides with long-chain fatty acids of app roximately 24-26 C atoms, while the narrow low-electron density region is formed by fully interdigitating, ceramides with a short free fatty ; acid chain of approximately 16 to 18 C atoms.