Membrane Electroconformational Changes: Progress in Theoretical Modelling of Electroporation and of Protein Protrusion Alteration

Abstract

Unambiguous, non-thermal effects of electric fields on biological cells have been reported by many investigators for moderate and strong fields (10 to 10 4 volt/cm; shorter exposure times for larger fields). This includes electroporation, which is believed due to transient and long lived pores in cell membranes. In order to develop theoretical models for such phenomena, we note that electrical interactions with cells are generally expected because of the heterogeneity of cells with respect to two basic parameters, electrical conductivity and electrical permittivity. This heterogeneity is particularly striking for the membrane/aqueous electrolyte interfaces, and leads to the general possibility of membrane forces. Possible responses to such forces include overall cell deformation, membrane indentations and membrane perforations (pores). Differential forces on the membrane and on membrane proteins are also possible, and include the possibility of altering protein protrusion from the membrane. To alter living cells, such changes must alter biochemical processes, e.g. transmembrane chemical fluxes. Here we describe progress in developing a quantitative theory of electroporation phenomena, and also a new possibility: changes in protrusion of membrane proteins. In the case of electroporation we emphasize predictions of measurable quantities, viz. the transmembrane voltage, U(t), and molecular transport, Ns, which is the total number of molecules of a given size and charge which cross a membrane due to a particular pulse. Modelling of both artificial planar bilayer membranes and cell membranes is possible. The artificial membranes are much simpler, and have therefore been the focus of initial theories. In the case of macromolecule protrusion, changes in protrusion could lead to alteration of binding site accessibility, and thereby provide a “signaling” possibility. Finally, by using “signal-to-(background + noise) ratio” (S/B+N) criteria, thresholds for electric field effects can be estimated. Electroporation has a large (S/B+N), while protein protrusion changes and other electroconformational change phenomena may involve much smaller values. By using the approximate criterion (S/B + N) ≈ 1, the smallest exposure for which an effect is expected can be estimated.