Polymer-induced leakage of cations from dioleoyl phosphatidylcholine and phosphatidylglycerol liposomes

The amphipathic polyacid, poly(2-ethylacrylic acid) (PEAA) has recently been shown to form fluctuating channels in patch-clamp measurements of phospholipid bilayers [J.C. Chung, D.J. Gross, J.L. Thomas, D.A. Tirrell, L.R. Opsahl-Ong, Macromolecules 29 (1996) 4636–4641.]. To explore this phenomenon further, we have quantified the PEAA-mediated pH-dependent release of sodium and calcium ions from phospholipid vesicles. Permeability to calcium increases linearly with polymer concentration and exponentially with decreasing pH. Permeabilization of negatively charged phosphatidylglycerol (PG) liposomes occurs to a similar extent and with a similar pH dependence to that of zwitterionic phosphatidylcholine (PC) liposomes, implying that a charge neutral species is responsible for the leakage. The pH dependence of leakage shows that the cooperative protonation of from three to five carboxylate anions is required for permeabilization. Such neutralization could result in a neutral segment of polymer chain of sufficient length to span the bilayer