The purpose of the research is to characterize a sharp thermotropic transition that has been demonstrated to occur in the membranes of mammalian cells. The effect of heating on plasma and nuclear membranes will be studied using a variety of biochemical, biophysical, and immunological techniques. Order parameters are to be obtained using spin label electron paramagnetic resonance techniques. Selected labels and fluorescent probes will characterize specific membrane regions and components. Values of lateral diffusion coefficients will be obtained by photo-bleaching experiments. Distribution, density and lateral mobility of H-2 and HLA antigens is to be determined using radiolabeled and fluorescent monoclonal antibodies. The effect of heating on cholesterol content of plasma membranes will be related to antibody binding. The information to be obtained from this research should suggest new approaches in clinical hyperthermia, suggest ways of improving drug delivery to solid tumors in chemotherapy, and to perhaps provide a rational, cellular basis for heat-immunotherapy.
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