The first aim of this research is to investigate the properties of phosphatidylcholines (PCs) and phosphatidylethanolamines (PEs) whose constituent fatty acyl chains are highly asymmetric in length. There are many important membrane components, such as the ceramide, sulfatide, ganglioside, and sphingomyelin molecules of nervous tissue, which contain two hydrocarbon chains of inequivalent length. The results of the research proposed in this project will help lead to an understanding of the effect of chain length asymmetry on the properties of lipids in natural membranes. It has recently been demonstrated that the asymmetric-chain phospholipid, 1-0-alkyl-2-acetyl-sn-glycero-3-phosphorylcholine, possesses important physiological functions as a platelet activating factor (PAF) and as an antihypertensive agent. A long term research project is being initiated in my laboratory with the objective of studing the physical and physiological properties of this important phospholipid. Thus, a second aim of this proposal is to begin this project by studying the physical properties of synthetic PAF and to attempt to isolate the receptor for PAF that has recently been shown to exist in human platelet membranes. Specifically, we propose to (1) investigate the properties of saturated mixed-chain PEs, C(18):C(18)PE through C(18):C(2)PE. This work will complement the studies that we have already carried out on the properties of saturated mixed-chain PCs. (2) to investigate the properties of binary mixtures of mixed-chain PCs and PEs with symmetric-chain phospholipids with particular emphasis on the mixing properties of the two lipid types as well as the possible existence of nonlamellar phases in the binary combinations; (3) to study the properties of synthetic PAF in comparison to those of C(18):C(2) PC. As C(18):C(2)PC is physiologically inactive, a comparison of the properties of these two lipids may serve to elucidate some of the important structural properties of PAF necessary for its physiological function; (4) to attempt to isolate the membrane receptor for PAF that has been shown to exist in human platelets by employing a combination of detergent solubilization and affinity chromatography. Principal techniques to be used are differential scanning calorimetry and densitometry, 31P-NMR, electron microscopy, quasi-elastic light scattering, Raman spectroscopy, detergent solubilization, and affinity chromatography.
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