The research proposed in this application is carried out with the objective of obtaining basic information about the effects of sphingomyelin on biological membrane structure and properties and how these effects might be related to aging and atherosclerosis in blood vessels. The work outlined will utilize multilamellar liposome dispersions, single lamellar vesicles of various sizes and monolayers formed at an air/water interface. Liposomes will be used to study both compositional asymmetry between opposite bilayer faces and compositional domains within the plane of the bilayer in sphingomyelin-phosphatidylcholine-cholesterol systems and systems containing amino phospholipids. Studies of bilayer permeability, availability of membrane lipids as substrates for enzymes in the aqueous phase, lipid-protein interactions and membrane structure as functions of composition and temperature will be undertaken in systems exhibiting compositional domains. Details of the interactions between these lipids will be examined directly using monolayer techniques. The information already obtained from our previous work on model systems and simple biological membranes such as that of the red blood cell and enveloped viruses will be applied to the studies on more the complex systems of rat heart myocytes and rat heart fibroblasts in culture. The effect of sphingomyelin content on the physiological (rate of beating), biochemical (enzyme activities) and transport activities will be correlated with the changes of membrane organization and dynamics of the lipid and protein components. Our preliminary results on rat myocytes show a strong correlation between the sphingomyelin to phosphatidylcholine mole ratio and these properties of cells and their plasma membranes. Special attention will be given to an evaluation of the contribution of the three regions of a sphingomyelin molecule (polar, hydrophobic and interface) to the various effects of sphingomyelins in model systems and in biological membranes.
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