The mechanism of membrane permeabilization by the antifungal heptaene macrolide amphotericin B (AmB) was investigated by using two different mercurysupported biomimetic membranes, namely a lipid self-assembled monolayer and a lipid bilayer tethered to the mercury surface through a hydrophilic spacer (tethered bilayer lipid membrane: tBLM). The disruptive permeabilization of a sterolfree mercury-supported lipid monolayer by low AmB concentrations, after a sufficiently long exposure to the macrolide, suggests a similar effect on the distal lipid monolayer of vesicular or bilayer lipid membranes. The notable permeabilization of a tBLM to Cd(II), with amalgam formation, by 0.6 ! M AmB complexed with sterols in a 1:3 molar ratio, as compared with the absence of any effect in the absence of sterols, suggests a direct participation of sterols in ion channel formation. The fact that the tBLM permeabilization requires the presence in solution of a freshly added AmB-sterol mixture and of Cd(II) or Ca2+ ions points out the notable role played by these divalent inorganic ions in the formation of AmB ion channels. Ion channels formed in a tBLM by AmB-ergosterol complexes are stable at physiological transmembrane potentials, whereas those formed by AmB-cholesterol complexes require application of nonphysiological transmembrane potentials for their stability.

Permeabilization of mercury-supported biomimetic membranes by amphotericin B and the role of calcium ions / Lucia Becucci;Massimo Innocenti;Silvano Bellandi;Rolando Guidelli. - In: ELECTROCHIMICA ACTA. - ISSN 0013-4686. - STAMPA. - 112:(2013), pp. 719-726. [10.1016/j.electacta.2013.09.027]

Permeabilization of mercury-supported biomimetic membranes by amphotericin B and the role of calcium ions

BECUCCI, LUCIA;INNOCENTI, MASSIMO;BELLANDI, SILVANO;
2013

Abstract

The mechanism of membrane permeabilization by the antifungal heptaene macrolide amphotericin B (AmB) was investigated by using two different mercurysupported biomimetic membranes, namely a lipid self-assembled monolayer and a lipid bilayer tethered to the mercury surface through a hydrophilic spacer (tethered bilayer lipid membrane: tBLM). The disruptive permeabilization of a sterolfree mercury-supported lipid monolayer by low AmB concentrations, after a sufficiently long exposure to the macrolide, suggests a similar effect on the distal lipid monolayer of vesicular or bilayer lipid membranes. The notable permeabilization of a tBLM to Cd(II), with amalgam formation, by 0.6 ! M AmB complexed with sterols in a 1:3 molar ratio, as compared with the absence of any effect in the absence of sterols, suggests a direct participation of sterols in ion channel formation. The fact that the tBLM permeabilization requires the presence in solution of a freshly added AmB-sterol mixture and of Cd(II) or Ca2+ ions points out the notable role played by these divalent inorganic ions in the formation of AmB ion channels. Ion channels formed in a tBLM by AmB-ergosterol complexes are stable at physiological transmembrane potentials, whereas those formed by AmB-cholesterol complexes require application of nonphysiological transmembrane potentials for their stability.
2013
112
719
726
Lucia Becucci;Massimo Innocenti;Silvano Bellandi;Rolando Guidelli
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Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/819910
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