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 sphingosine-d28 deuterated N-lignoceroyl-d-erythro-sphingosine (ceramide [NS]), we compare the structure and dynamics of both chains of that lipid in biologically relevant mixtures using X-ray diffraction, 2 H NMR analysis, 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 current understanding of the skin lipid barrier, where an extended ceramide [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.

Department of Chemical Science Tata Institute of Fundamental Research Dr Homi Bhabha Road Colaba Mumbai 400 005 India

Institute of Medical Physics and Biophysics University of Leipzig Härtelstr 16 18 04275 Leipzig Germany

Skin Barrier Research Group Faculty of Pharmacy in Hradec Králové Charles University Akademika Heyrovského 1203 50005 Hradec Králové Czech Republic

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