Inversion of Membrane Surface Charge by Trivalent Cations Probed with a Cation-Selective Channel

Abstract

We demonstrate that the cation-selective channel formed by gramicidin A can be used as a reliable sensor for studying the multivalent ion accumulation at the surfaces of charged lipid membranes and the “charge inversion” phenomenon. In asymmetrically charged membranes with the individual leaflets formed from pure negative and positive lipids bathed by 0.1 M CsCl solutions the channel exhibits current rectification which is comparable to that of a typical n/p semiconductor diode. We show that even at these highly asymmetrical conditions the channel conductance can be satisfactorily described by the electrodiffusion equation in the constant field approximation but, due to predictable limitations, only when the applied voltages do not exceed 50 mV. Analysis of the changes in the voltage-dependent channel conductance upon addition of trivalent cations allows us to gauge their interactions with the membrane surface. The inversion of the sign of the effective surface charge takes place at the concentrations which correlate with the cation size. Specifically, these concentrations are close to 0.05 mM for lanthanum, 0.25 mM for hexaamminecobalt, and 4 mM for spermidine.

Investigation of Ion Channel Activities of Gramicidin A in the Presence of Ionic Liquids Using Model Cell Membranes

“…3B , the latter effect is greater. Positive charges on the membrane surface significantly decrease the rate of ion flux due to cation depletion near gA channels 32 34 . To compare the effects of different ILs, we analyzed the ion permeability rate as a function of IL concentration at a fixed time, i.e., 2 ms, after mixing liposomes with Tl + .…”

Experimental demonstration of charge inversion in a protein channel in the presence of monovalent cations

“…As far as we know charge inversion has been reported in presence of salts of multivalent cations in systems of membrane channels [3][4][5], but only this is the first example concerning monovalent cations. Previous studies of charge inversion in systems in which the charge is pH-dependent mention specific adsorption of metal cations and correlation effects as potential candidates to explain charge inversion observations [10].…”

“…An extreme case occurs when interfacial charges attract counterions in excess of their own nominal charge, thus leading to an effective charge inversion of the system [1,2]. This phenomenon has been reported in diverse systems that are in contact with an aqueous solution containing multivalent ions: lipid vesicles, colloids, polyelectrolytes, Langmuir monolayers, membranes, nanopores and ion channels among others [1][2][3][4][5]. Here, we focus on the bacterial channel OmpF of E. coli [6] to report experimental evidence of charge inversion in presence of monovalent cations.…”

Multivalent ions and biomolecules: Attempting a comprehensive perspective

“…[408] An interesting approach to estimate the affinity of (multivalent) cations to membranes is to use channel proteins inserted into reconstituted lipid systems. Gurnev et al [409] employed a cation-selective channel to estimate the extent of charge inversion of lipid membranes of multivalent cations, revealing that La 3 + cations were more efficient at inverting membrane surface charge than hexaamminecobalt and spermidine. The effect of another trivalent cation was demonstrated by Ermakov et al [410] who showed a pronounced compaction of brain PS upon binding of Gd 3 + .…”