期刊
MEMBRANES
卷 12, 期 11, 页码 -出版社
MDPI
DOI: 10.3390/membranes12111166
关键词
lantibiotic; nisin; ion channel; lipid bilayers; cardiolipin; membrane dipole potential; phloretin
类别
资金
- Russian Foundation of Science
- [22-15-00417]
This study focused on the action of lantibiotic nisin on phospholipid membranes, revealing that its effectiveness depends on the membrane composition and can exert its anti-tumor activity by forming ion pores. The preferential interaction of nisin with cardiolipin-enriched bilayers was observed, and small molecules were found to enhance the membrane activity of nisin.
This study was focused on the action of lantibiotic nisin on the phospholipid membranes. Nisin did not produce ion-permeable pores in the membranes composed of DOPC or DOPE. The introduction of DOPS into bilayer lipid composition led to a decrease in the threshold detergent concentration of nisin. An addition of nisin to DOPG- and TOCL-enriched bilayers caused the formation of well-defined ion pores of various conductances. The transmembrane macroscopic current increased with the second power of the lantibiotic aqueous concentration, suggesting that the dimer of nisin was at least involved in the formation of conductive subunit. The pore-forming ability of lantibiotic decreased in the series: DOPC/TOCL approximate to DOPE/TOCL >> DOPC/DOPG >= DOPE/DOPG. The preferential interaction of nisin to cardiolipin-enriched bilayers might explain its antitumor activity by pore-formation in mitochondrial membranes. Small natural molecules, phloretin and capsaicin, were found to potentiate the membrane activity of nisin in the TOCL-containing membranes. The effect was referred to as changes in the membrane boundary potential at the adsorption of small molecules. We concluded that the compounds diminishing the membrane boundary potential should be considered as the potentiator of the nisin pore-forming ability that can be used to develop innovative formulations for anticancer therapy.
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