Electrical Aspects of Membrane Permeabilization by New Polycationic Peptides Derived from the Cry11Bb Protoxin

Abstract

The permeabilization of mitochondrial and plasma membranes by synthetic polycationic peptides derived from the Cry11Bb protoxin was studied. The peptides were designed with the aim to further study of their antimicrobial and anticancer activities. It was observed that the membrane permeabilizing activity of these polycationic peptides strongly increased by the transmembrane potential (minus inside). This phenomenon was confirmed by the study of the artificial planar membrane permeabilization: applying 50 mV to the planar membrane (minus to the trans side) during 30 sec induced time-dependent increase in the transmembrane current in the presence of a peptide added to the cis side, while subsequent application of the opposite potential caused its decrease. We also observed that the activation of the cell suicide mechanism, which partially revealed in phosphatidylserine exposure at the cell surface, significantly increased the plasma membrane permeabilization by polycationic peptides. Some peptide topology characteristics, such as the value and the orientation of the electrical dipole moment(s) interacting with the membrane dipole potential seem to also be important factors influencing the membrane-permeabilizing activity of polycationic peptides. In general, our data are consistent with the concept that various electrical properties of biomembranes (the transmembrane potential, membrane dipole potential and the surface charge) might explain at least partially certain selectivity of antimicrobial and anticancer activities of many natural and synthetic polycationic peptides. (Financial support: Colciencias (Colombia) research grant #111840820380).