Fluorescence Studies Of Biophysical Properties Of Polyun

神经元和视网膜组织的膜含有大量含有一个或两个长链多不饱和酰基链的磷脂。二十二碳六烯酸（缩写为DHA或22：6 n-3）是这些组织中主要的多不饱和酰基链。这项研究是针对确定的多不饱和磷脂，特别是那些含有22：6 n-3酰基链的G蛋白偶联受体信号转导的调制的分子基础。研究还集中在这些磷脂对急性暴露于乙醇的反应上。荧光能量转移（FRET）研究已经证明了在含有di 16：0 PC和di 22：6PC加胆固醇的双层中的横向结构域形成，其依赖于胆固醇和视紫红质两者的存在。继续FRET研究，沿着与原子力显微镜和差示扫描量热法，正在追求，以表征横向域形成的双层22：6 n-3含有脂质。酰基链自由体积和曲率应力都被认为是调节膜蛋白功能的双层性质。实验表明，这两个属性之间的反比关系，这表明他们可能有相反的影响，相对于调节蛋白质的功能。最近的研究表明，在调节膜蛋白功能的主要属性将取决于膜脂质组成。胆固醇-鞘磷脂相互作用被认为是生物膜中结构域或筏形成的驱动力。我们对di 16：0 PC-di 22：6PC-胆固醇-视紫红质系统的研究表明，侧域形成的更普遍的驱动力是胆固醇-脂质相互作用，蛋白质-脂质相互作用也可能是一个促成因素。为了阐明磷脂组成在结构域形成中的作用，研究了胆固醇分配到确定的脂质组成的双层中。建立了一种测定胆固醇在脂质双层中分配的新方法。这些研究表明，胆固醇分配是由磷脂头基和酰基链组成。多不饱和酰基链在降低脂质膜中胆固醇水平方面是最有效的，而反式脂肪酸增加膜胆固醇含量。这些研究是重要的，在开发和理解的作用脂质组成一般和22：6 n-3酰基链，特别是在域的形成，膜蛋白功能的调制，胆固醇在细胞膜的异质性分布，以及健康的好处和赤字与多不饱和脂肪酸和反式脂肪酸，分别。

The membranes of neuronal and retinal tissue are high in phospholipids containing one or two long chain polyunsaturated acyl chains. Docosahexaenoic acid (abbreviated DHA or 22:6n-3) is the major polyunsaturated acyl chain in these tissues. This study is directed towards determining a molecular basis for the modulation of G protein-coupled receptor signaling by polyunsaturated phospholipids, in particular those containing 22:6n-3 acyl chains. Studies are also focused on the response of these phospholipids to the acute exposure to ethanol. Fluorescence Energy Transfer (FRET) studies have demonstrated lateral domain formation in bilayers containing di16:0PC and di22:6 PC plus cholesterol, which was dependent on the presence of both cholesterol and rhodopsin. Continued FRET studies, along with atomic force microscopy and differential scanning calorimetry, are being pursued in order to characterize lateral domain formation in bilayers of 22:6n-3 containing lipids. Both acyl chain free volume and curvature stress have been invoked as bilayer properties, which modulate membrane protein function. Experiments indicate an inverse relationship between these two properties, suggesting that they may have opposite effects with respect to modulating protein function. Recent studies suggest that the dominant property in modulating membrane protein function will depend on the membrane lipid composition. Cholesterol-sphingomyelin interactions are thought to be the driving force for domain or raft formation in biological membranes. Our studies of the di16:0PC-di22:6PC-cholesterol-rhdopsin system demonstrate that a more general driving force for lateral domain formation is cholesterol-lipid interaction and that protein-lipid interaction can also be a contributing factor. In order to clarify the role of phospholipid composition in domain formation, the partitioning of cholesterol into bilayers of defined lipid composition was studied. A novel method of measuring cholesterol partitioning into lipid bilayers was developed. These studies show that cholesterol partitioning is determined by both phospholipid head group and acyl chain composition. Polyunsaturated acyl chains are among the most effective in reducing the level of cholesterol in lipid membranes, while trans fatty acids increase membrane cholesterol content. These studies are important in developing and understanding the role lipid composition in general and 22:6n-3 acyl chains in particular, in domain formation, the modulation of membrane protein function, the heterogeneous distribution of cholesterol in cell membranes, and the health benefits and deficits associated with polyunsaturated fatty acids and trans fatty acids, respectively.