This proposal continues and expands current research in the general area of the bio-organic chemistry of lipids with heavy emphasis on understanding the behavior of giant vesicles. Giant vesicles are cell- sized structures composed of natural or synthetic lipid bilayers. Preliminary experiments have shown the occurrence of """"""""cytomimetic"""""""" events (e.g. fusion, fission, endocytosis, budding, aggregation, birthing, and wound healing) when giant vesicles are subjected to specific chemical or physical perturbations. Since these cell-like processes can be visualized by phase-contrast microscopy an opportunity now exists of directly monitoring their time-course and mechanisms. Giant vesicles have a distinct advantage over living cell membrane in that the former allows a controllable composition and morphology. Thus, one can systematically vary giant vesicles via their cholesterol content, type of phospholipid or phospholipid mixture, presence of a fusogenic agent, electric charge, etc. By this means membrane alterations can be related to molecular structure. This information is important to a variety of topics of bio-medical concern including liposomal drug delivery; endocytosis of DNA in transfection processes; transmembrane signaling by hormones; adhesion of cancer cells, platelets, etc.; fusion of viral membranes with plasma membrane; and fertilization. Specific on-going or planned experiments include: measure the rotational rate of adhered vesicles; study vesicle adhesion to cancer cells mediated by a synthetic mannose phosphonate/cholesterol conjugate; assess the fusogenic ability of phosphatidylethanol, gemini surfactants, and polymeric systems; use """"""""light intensity distributions"""""""" to monitor membrane layering; determine the rate of membrane healing after physical injury; take advantage of volume and surface area measurements to track the fate of lipid during birthing and fusion processes; and examine vesicle/cell interchange of lipid by epifluorescent microscopy.
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