The Sphingosine and Acyl Chains of Ceramide [NS] Show Very Different Structure and Dynamics Challenging Our Understanding of the Skin Barrier.

The lipid phase of the uppermost human skin layer is thought to comprise highly rigid lipids in an orthorhombic phase state to protect the body against the environment. By synthesizing sphin-gosine- d 28 deuterated N- lignoceroyl-D- erythro- sphingosine (cerami-de [NS]), we compare the structure and dynamics of both chains of that lipid in biologically relevant mixtures using X-ray diffraction, 2 H NMR and infrared spectroscopy. Our results reveal a substantial fraction of sphingosine chains in a fluid and dynamic phase state at physiological temperature. These findings prompt revision of our cur-rent understanding of the skin lipid barrier, where an extended cera-mide [NS] conformation is preferred and a possible domain structure is proposed. Mobile lipid chains may be crucial for skin elasticity and the translocation of physiologically important molecules.