Electrostatic properties of membranes containing acidic lipids and adsorbed basic peptides: Theory and experiment

The interaction of heptalysine with vesicles formed from mixtures of the ac idic lipid phosphatidylserine (PS) and the zwitterionic lipid phosphatidylc holine (PC) was examined experimentally and theoretically. Three types of e xperiments showed that smeared charge theories (e.g., Gouy-Ghapman-Stern) u nderestimate the membrane association when the peptide concentration is hig h. First, the zeta potential of PC/PS vesicles in 100 mM KCI solution incre ased more rapidly with heptalysine concentration (14.5 mV per decade) than predicted by a smeared charge theory (6.0 mV per decade). Second, changing the net surface charge density of vesicles by the same amount in two distin ct ways produced dramatically different effects: the molar partition coeffi cient decreased 1000-fold when the mole percentage of PS was decreased from 17% to 4%, but decreased only 10-fold when the peptide concentration was i ncreased to 1 mu M. Third, high concentrations of basic peptides reversed t he charge on PS and PC/PS vesicles. Calculations based on finite difference solutions to the Poisson-Boltzmann equation applied to atomic models of he ptalysine and PC/PS membranes provide a molecular explanation for the obser vations: a peptide adsorbing to the membrane in the presence of other surfa ce-adsorbed peptides senses a local potential more negative than the averag e potential. The biological implications of these "discreteness-of-charge" effects are discussed.