The immediate goal is to test the hypothesis that the local bilayer instabilities, caused by the stored bending energy from molecular mismatching of membrane lipids, control certain membrane functions. From preliminary reports, this type of control mechanism, previously neglected, is important in the functions of biomembranes. This proposal is to place the existing qualitative correlation on a semi-quantitative basis, to rigorously test this hypothesis. The proposal consists of 4 projects. 91) to calculate the spontaneous curvature and the bending energy of a number of mixed lipid bilayers from the physical properties of the components, and quantitatively correlate them with the phase behavior (bilayer stability) of these lipid systems. A number of common membrane phospholipids, lysophospholipids, diacylglycerols and cholesterol will be used. The onset of the appearance of non-bilayer phases, which is an indication of the peak of the bending energy, will be detected by x-ray diffraction, P-31 NMR and freeze fracture electron microscopy. (2) to continue the monitoring of lipid transfer, calcium transport by Ca-ATpase and C, as functions of the bending energy. (3) to measure directly the """"""""tightness"""""""" of molecular packing predicted by the bending energy hypothesis, using fluorescent probes and H2-NMR. (4) to investigate the mechanism of controlling cell proliferation and oncogene expression by the physical properties of phosphatidic acids. The long term goal is to understand how the various membrane functions are affected by the well regulated diversity of membrane lipids. The elucidation of the control mechanism would allow the manipulation of function and dysfunction of cell membranes.
