The Chain Length of Free Fatty Acids Influences the Phase Behaviour of Stratum Corneum Model Membranes: A 2h-NMR and IR Investigation

Abstract

Stratum corneum (SC), the outermost layer of mammal epidermis, is the main element of skin impermeability. It is formed by corneocytes embedded in a lipid matrix, which is mostly constituted by ceramides (Cer), free fatty acids (FFA) and cholesterol (Chol), organized in two coexisting crystalline lamellar phases. The diffusion of substances across the SC is proposed to proceed mainly via the intercellular lipid matrix and therefore, the understanding of the lipid matrix structure and of the molecular interactions dictating it is crucial for comprehending and controlling the penetration of substances through the skin. The aim of this work is to determine the impact of FFA chain length on the phase behaviour of SC model lipid membranes, using solid-state deuterium NMR and IR spectroscopy. We studied ternary mixtures of N-lignoceroyl-D-erythro-sphingosine (Cer24), cholesterol, and palmitic (FFA16) or lignoceric (FFA24) acid in equimolar ratio. Our studies revealed that the phase behaviour of Cer24/FFA/Chol ternary mixtures is deeply affected by the length of the FFA. We found the formation of phase-separated crystalline lipid domains when using palmitic acid while the use of lignoceric acid results in a more homogeneous mixture. FFA24 solid phase, observed in the mixture at low temperature, gains motional freedom at temperature lower than expected for such a long-chain FFA. In addition, mixtures with lignoceric acid form a gel phase, a very unusual feature for SC model mixtures. The reduction of FFA and ceramide chain length is reported in atopic eczema and atopic dermatitis patients. Coupling the reduction in lipid chain length with an altered phase behavior, such as less homogeneous lipid mixing, would constitute a major step forward in our understanding of the skin barrier.