The interaction of dipole modifiers with polyene-sterol complexes.

Peter Butko,Olga S Ostroumova,Evgeny G Chulkov,Ludmila V Schagina,Svetlana S Efimova

doi:10.1371/journal.pone.0045135

Abstract

Recently, we showed that the effect of dipole modifiers (flavonoids and styrylpyridinium dyes) on the conductance of single amphotericin B (AmB) channels in sterol-containing lipid bilayers primarily resulted from changes in the membrane dipole potential. The present study examines the effect of dipole modifiers on the AmB multi-channel activity. The addition of phloretin to cholesterol-containing membranes leads to a significant increase in the steady-state AmB-induced transmembrane current. Quercetin significantly decreases and RH 421 increases the current through ergosterol-containing bilayers. Other tested flavonoids and styrylpyridinium dyes do not affect the channel-forming activity of AmB independently on the sterol composition of the bilayers. The effects obtained in these trials may instead be attributed to the direct interaction of dipole modifiers with AmB/sterol complexes and not to the effect of dipole potential changes. The presence of double bonds in the Δ7 and Δ22 positions of sterol molecules, the number of conjugated double bonds and amino sugar residues in polyene molecules, and the conformation and adsorption plane of dipole modifiers are important factors impacting this interaction.

Highlights

In recent years, there has been growing interest in understanding the role that lipid bilayer properties have on the channelforming action of various membrane-active biomolecules
As sterols are constitutive components of the plasma membrane, and their presence defines the specificity of action for many pharmacological agents, the study of the channel-forming activity of toxins and antimicrobial compounds in the lipid bilayers of different sterol composition is important for predicting the effects of these compounds on different cell types
It can be noted that: (i) phloretin significantly increases the steady-state current (I‘) through Chol-containing bilayers, but it has no effect on Erg-containing membranes; (ii) quercetin does not affect I‘ in Chol-containing membranes, but it decreases I‘ in Erg-containing bilayers; and (iii) RH 421 has no effect on I‘ in Chol-containing membranes, whereas it significantly increases the steady-state current through Erg-containing bilayers

Summary

Introduction

There has been growing interest in understanding the role that lipid bilayer properties have on the channelforming action of various membrane-active biomolecules.

Results

Conclusion