Surface charge effects upon membrane transport processes: the effects of surface charge on the monensin-mediated transport of lithium ions through phospholipid bilayers studied by 7Li-NMR spectroscopy.

Addition of monensin to preparations of large unilamellar vesicles prepared from egg-yolk phosphatidylcholine (egg PC) or egg PC containing 5% phosphatidylserine (PS-) or cetylpyridinium (CP+) ions in lithium chloride solution allows the transport of Li+ ions to be monitored by an NMR magnetisation transfer technique. The kinetics of the transport are followed as a function of the metal ion and monensin concentrations and are compatible with a model in which one monensin molecule transports one Li+ ion. The data allow the extraction of the rate constants for the association and dissociation of the monensin-Li+ complex in the water/membrane interfaces and the evaluation of the stability constants for complex formation in the interfaces. Placing positive charge (CP+) on the membrane surface reduces the formation rate by a factor of about three but hardly alters the dissociation rate. Placing negative charge (PS-) on the membrane surface hardly alters the formation rate but speeds the dissociation rate by about a factor of three. Data from relaxation times of 7Li+ inside the vesicles and from the total enclosed volumes as the vesicles are formed, point to appreciable Li+ surface interactions that increase as the charge on the surface is made more negative. The size of the vesicles formed by the dialytic detergent removal technique increases with the surface charge. The results support a view that enzyme-phospholipid or substrate-phospholipid interactions could play an important role in determining the efficacity of action of membrane bound enzymes. The relevance of the results in the role of Li+ in the control of manic depression is also discussed.