The objective of this project is to examine the electrostatic potentials on the production of second messengers. The hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2), a lipid located on the cytoplasmic surface of cell membranes, produces inositol 1,4,5-triphosphate (IP3) and diacylglycerol (DG). IP3 induces the release of calcium; DG activates a protein kinase C. Dr. McLaughlin will carry out a number of projects including: 1) studying the binding of polyvalent cations like neomycin to PIP2; 2) labelling the hydrocarbon tails of PIP2 and making fluorescence energy transfer measurements; 3) studying the effect of electrostatic potentials on the ability of calcium to activate a polyphosphoinositide-specific phospholipase C; and 4) continuing theoretical and experimental studies of the role of surface potentials and cooperativity in the binding of polyvalent cations to monovalent anionic lipids in bilayer membranes. Although very few biophysicists are working in this area and little information is available about the physical factors that influence the production and mechanism of action of these second messengers, there is a great deal of evidence present for believing that one of these factors is the electrostatic potential produced by charged lipids such as phosphatidylserine.
