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

神经酰胺-1-磷酸已被认为是一种重要的信号分子，调节多种重要的生理功能，但其物理化学性质以及这些性质如何与其不同的生理功能相关联还没有详细的报道。各种环境因素的影响，如盐浓度、二价阳离子的存在和其他脂质的存在，将使用广泛的现代和复杂的结构、热力学和形态方法进行研究。拟议的研究大大得益于两个研究小组的互补专业知识。神经酰胺-1-磷酸介导的信号事件在许多情况下与胆固醇/鞘磷脂富集域(“RAFT”)有关。虽然与阳离子物种的相互作用预计会导致液体有序脂筏结构域内形成更高阶域，但一旦排斥力占优势，这些有序结构很可能会解体。高度有序结构域的形成很可能会限制与蛋白质的相互作用，即头基的功能类似于静电开关。提示神经酰胺-1-磷酸和磷脂酰肌醇在一定条件下是共定位的。因此，提出的研究旨在探索这些重要信号分子之间的相互作用。

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.