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. 1999 Dec;77(6):3176–3188. doi: 10.1016/S0006-3495(99)77148-1

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

D Murray 1, A Arbuzova 1, G Hangyás-Mihályné 1, A Gambhir 1, N Ben-Tal 1, B Honig 1, S McLaughlin 1
PMCID: PMC1300588  PMID: 10585939

Abstract

The interaction of heptalysine with vesicles formed from mixtures of the acidic lipid phosphatidylserine (PS) and the zwitterionic lipid phosphatidylcholine (PC) was examined experimentally and theoretically. Three types of experiments showed that smeared charge theories (e.g., Gouy-Chapman-Stern) underestimate the membrane association when the peptide concentration is high. First, the zeta potential of PC/PS vesicles in 100 mM KCl solution increased 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 distinct ways produced dramatically different effects: the molar partition coefficient 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 increased to 1 microM. Third, high concentrations of basic peptides reversed the charge on PS and PC/PS vesicles. Calculations based on finite difference solutions to the Poisson-Boltzmann equation applied to atomic models of heptalysine and PC/PS membranes provide a molecular explanation for the observations: a peptide adsorbing to the membrane in the presence of other surface-adsorbed peptides senses a local potential more negative than the average potential. The biological implications of these "discreteness-of-charge" effects are discussed.

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Selected References

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