AMPHIPHILIC ASSOCIATION STRUCTURES 167 Electron microscopy has provided the basis for the layered structure suggested by Elias (23) (Figure 11), citing the ceramides as the structure-forming elements. Later, our group could show the fatty acids to be the essential compounds for the layered structure (24) and that a considerable part of the lipids are located in the space between the methyl groups. The key to the role of the free fatty acids lies with the variation of their association structures with the pH (Figure 12). At low pH the acids exist as such and show no interaction with water, and at high pH they are ionized soaps that dissolve in water, forming a miceliar solution (compare Figure 2). At intermediate pH values, like those of the skin (4.5-6), the acids are partially ionized, and this mixture of soap and acid forms a lameliar liquid crystal, provided unsaturated fatty acids are present (Layered Structure, Figure 12). This acid/soap lameliar liquid crystal accommodates the re- maining stratum corneum lipids into a structure similar to Elias' model (Figure 11). The "phase diagram" (Figure 12) has several features, but one of them is of decisive importance for cosmetic applications. The diagram shows the liquid crystal layered structure to be changed to a crystal structure when the water content is reduced below a certain level (Liquid crystal/Crystal, Figure 12). This change has a drastic effect both on the appearance and smoothness of the skin, and a discussion is justified. The lipids, at high water content, are in the form of a liquid crystal, a transparent vehicle similar in consistency to soft butter. It is expected and natural that such a vehicle in the skin will make it smooth and pleasant the difference in texture of the skin when the lipids are in this "ointment" form and when in the form of a dry crystal- line powder is obvious. But the liquid crystalline arrangement is also important because of its optical properties. It is birefringent between crossed polarizers (Figure 13). The difference in the appearance of the skin when the reflected light comes from such a layer and from a dry powder is self-evident. With this fact in mind, an explanation is straightforward: why skin in high relative humidity looks glossy and appealing while under dry conditions it has a dry, "scaly" appearance. The essential factor is that the high water content results in a liquid crystal organization of the lipids the higher water content per se is not important for the appearance. This has recently been shown (25) in an investigation on the role of mois- turizer by glycerol. The action of glycerol was not found to attract water to the skin from the surrounding atmosphere, and it had no significant effect on the evaporation of water from a stratum corneum lipid model. Instead, the presence of glycerol prevented the crystallization of the lipids when the water Cholesterol Ceramide 61ucosyl- OIFFERENTIAIEO CELLS INIERCELLULAR LAYERED STRUCTURE REGION Figure 11. Elias model (23) for the structure of the stratum corneum lipids.

168 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS Acid High pH: Aqueous Soap Solution Water Soap Increasing Soap Figure 12. The free fatty acid/soap lamellar liquid crystal as base for the stratum corneum lipids requires a minimum water content for stability. Below that water concentration lipid crystals form. content was reduced. This is a new role for a "moisturizer," and it is likely that this new concept, which is easily quantified, will bring new development in the area of cosmetic additives. The layered liquid crystalline structure per se is also the main factor in the barrier to water transport. It has recently been demonstrated that the specific lipid in the struc- ture is not important for the water barrier (26) a layered structure of only the partly saponified free fatty acids forms a satisfactory barrier (27). In this context, it should be noticed that a stratum corneum lipid composition of only saturated chains leads to a crystalline structure only. A model structure with crystalline lipids showed extremely fast water evaporation (28), a result in excellent agreement with the in vivo experiences under the essential fatty acid deficiency syndrome (29-30). This liquid crystalline structure of the stratum corneum lipids makes it possible to outline the interaction between the association structures in different ointments (earlier sections) and the stratum corneum.