Plasma membranes are essential to both the structure and function of mammalian cells. The first unifying paradigm of membrane structure, the Fluid Mosaic Model, is no longer considered adequate to describe the many non-homogeneous lipid structures that have been observed in both natural and model membranes over the past approximately thirty years. The field of membrane biophysics now appreciates that the complex mixture of different lipid species found in natural membranes produces a range of

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... namic, laterally segregated, non-homogeneous structures which exist on time scales ranging from microseconds to minutes. When sphingomyelin (SM), POPC and cholesterol are all present in a bilayer there is wide range of compositional ratios where the bilayer consists of a coexistence between two fluid phases designated liquid ordered (lo) and liquid disordered (ld). The lo phase is cholesterol-rich phase characterized by relatively high molecular order and slow rotational and translational motion, while the ld phase generally has low molecular order and relatively rapid rotational and translational motion. The driving force for the formation of these two phases is the ability of cholesterol to form favorable van der Waals contacts with the two saturated acyl chains on PSM and the one saturated acyl chain on POPC. The ternary system is an important model system for examining the physical properties and functional implications of co-existing lo and ld phases. However, it does not include one of the most significant compositional variables found in many important mammalian ii membranes. Membranes in the nervous system contain high concentrations of the highly polyunsaturated fatty acid docosahexaenoic acid (DHA), which contains 22 carbons and 6 double bonds. A wide range of experimental evidence shows that DHA-containing phospholipids are important for optimal performance of a number of membrane signaling systems and membrane protein functions. The goal of this study is to determine how addition of a DHA-containing phospholipid, PDPC alters the biologically important lo and ld co-existence region. iii