Ion Channels Induced by Antimicrobial Agents in Model Lipid Membranes are Modulated by Plant Polyphenols Through Surrounding Lipid Media
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The potential therapeutic applications of plant polyphenols in various neurological, cardiovascular, metabolic and malignant disorders determine the relevance of studying the molecular mechanisms of their action on the cell membranes. Here, the quantitative changes in the physical parameters of model bilayer lipid membranes upon the adsorption of plant polyphenols were evaluated. It was shown that butein and naringenin significantly decreased the intrinsic dipole potential of cholesterol-free and cholesterol-enriched membranes. Cardamonin, 4′-hydroxychalcone, licochalcone A and liquiritigenin demonstrated the average efficiency, while resveratrol did not characterized by the ability to modulate the bilayer electrostatics. At the same time, the tested polyphenols affected melting of phospholipids with saturated acyl chains. The effects were attributed to the lipid disordering and a promotion of the positive curvature stress. According to DSC data and results of measurements of the threshold voltages that cause bilayer breakdown licochalcone A is the most effective agent. Furthermore, the role of the polyphenol induced changes in the electric and elastic properties of lipid host in the regulation of reconstituted ion channels was examined. The ability of the tested polyphenols to decrease the conductance of single ion channels produced by the antifungal cyclic lipopeptide syringomycin E was in agreement with their effects on the dipole potential of the lipid bilayers. The greatest effect of licochalcone A on the steady-state membrane conductance induced by the antifungal polyene macrolide antibiotic nystatin correlated with its greatest efficacy to induce the positive curvature stress. We also found that butein and naringenin bind specifically to a single pore formed by α-hemolysin from Staphylococcus aureus.
KeywordsPolyphenols Lipid bilayers Ion channels Lipid melting Membrane dipole potential Curvature stress
Authors thank Prof. Ludmila Schagina and Valery Malev for fruitful discussion.
This study was funded by the RFBR (#16-04-00806) and the Russian Foundation of Science (# 17-74-10137) (investigation of polyphenol-lipid structures).
Compliance with Ethical Standards
Conflict of interest
The authors declare that they have no conflict of interest.
This article does not contain any studies with human participants or animals performed by any of the authors.
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