Investigation of the influence and function of different ceramide subspecies to the nanostructure and the dynamic of Stratum corneum lipid model systems

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Ceramides belong to a unique class of lipids, which differs significantly from other lipids classes. The polar head group of the ceramides are considerably less polar; the hydrophobic region is always formed by two different hydrocarbon chains, whereby one chain can be substantially longer than the other. The intercellular ceramides are essentially responsible for the barrier function of the Stratum corneum (SC). How those physico-chemically variable and dermatologically interesting lipids impact the structural organisation of the SC and therefore, the epidermal barrier is to a large extent unknown. The intended experiments will fundamentally contribute to the clarification which ceramide subclass is essential for the SC and are able to intensify the epidermal barrier. Especially the role of the polar head group of the ceramides (number and position of hydroxyl groups) will be studied. Furthermore, substances, which can be applied to enhance the penetration of drugs through this barrier, will be studied. The expertise of the work groups (WG) Huster and Brezesinski within this joint project will for the first time enable the study of the molecular dynamics of the ceramides in model bilayers (WG Huster) and allow for the investigation of the interaction of the polar head group of the ceramides with pharmaceutically relevant penetration enhancers (WG Brezesinski). This will substantially widen the knowledge of previous studies concerning the nanostructure of the ceramides and ceramide-containing SC lipid model membranes (WG Neubert). Additionally, molecular dynamic simulations (MD-Simulation) will be integrated as a theoretically method to optimally verify the experimentally received findings. For such studies both specifically deuterated as well as perdeuterated ceramides are indispensible; those have to be laboriously synthesised by the WG Dobner.