Structural and morphological characterization of ceramide-1-phosphate model membranes

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Ceramide-1-phosphate has been identified as an important signaling molecule that mediates a large variety of important physiological functions, but its physicochemical properties and how these properties are linked to its diverse physiological functions have not been detailed. The influence of a variety of environmental factors like salt concentration, presence of divalent cations and presence of other lipids will be investigated by using broad range of modern and sophisticated structural, thermodynamic and morphological methods. The proposed research strongly benefits from the complementary expertise of the two research groups. Ceramide-1-phosphate mediated signaling events have been associated in many cases with cholesterol/sphingolipid enriched domains (“rafts”). While interaction with cationic species is expected to result in the formation of higher order domains within the liquid-ordered lipid raft domain, it is likely that these ordered structures disintegrate once repulsive forces become dominant. The formation of highly ordered domains would most likely restrict the interaction with proteins, i.e., the headgroup would function like an electrostatic switch. It is suggested that ceramide-1-phosphate and phosphoinositides are co-localized under certain circumstances. Therefore, the proposed research aims to explore the interaction between these important signaling molecules.