Phase Behavior of Stratum Corneum Lipid Mixtures Based on Human Ceramides: The Role of Natural and Synthetic Ceramide 1

Abstract

In a recent study the lipid phase behavior of mixtures of human ceramides, cholesterol, and free fatty acids has been examined. We observed in cholesterol: human ceramide mixtures a prominent formation of the 12.8 nm lamellar phase (referred to as the long periodicity phase). Addition of free fatty acids promoted the formation of a 5.6 nm lamellar phase (referred to as the short periodicity phase) and increased the subpopulation of lipids forming a fluid phase. In this study we focused on the role of human ceramide 1, as the presence of this ceramide appeared to be crucial for proper lipid phase behavior in mixtures prepared with ceramide isolated from pig stratum corneum. In order to do this, mixtures of cholesterol and free fatty acids were prepared with human ceramides, in which natural human ceramide 1 was replaced by either synthetic CER1-linoleate (CER1-lin), or CER1-oleate (CER1-ol), or CER1-stearate (CER1-ste). After substitution of natural human ceramide 1 by synthetic ceramide 1 the following observations were made. (i) In the presence of synthetic CER1-ste no long periodicity phase and no liquid phase could be detected. (ii) In the presence of HCER1-ol a liquid phase was more prominently formed than in the presence of HCER1-lin. (iii) In cholesterol:human ceramide mixtures in the presence of CER1-lin the long periodicity phase was more prominently present than in the presence of CER1-ol. (iv) In the presence of CER1-ste neither a long periodicity phase nor a liquid lateral packing could be detected. The results of these studies further indicate that for the formation of the long periodicity phase a certain (optimal) fraction of lipids has to form a liquid phase. When the fraction forming this liquid phase is either too low or too high, the formation of the short periodicity phase is increased at the expense of the formation of the long periodicity phase. Based on the results of this and previous studies we offer an explanation for the deviation in lipid organization in diseased and in dry skin compared to normal skin.