Molecular organization of antifungal antibiotic amphotericin B in lipid monolayers studied by means of Fluorescence Lifetime Imaging Microscopy

Wieslaw I. Gruszecki, Rafał Luchowski, Mariusz Gagoś, Marta Arczewska, Pabak Sarkar, Monika Hereć, Beata Myśliwa-Kurdziel, Kazimierz Strzałka, Ignacy Gryczynski, Zygmunt Gryczynski

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

Amphotericin B (AmB) is a life-saving polyene antibiotic used to treat deep-seated mycotic infections. Both the mode of therapeutic action as well as toxic side effects are directly dependent on molecular organization of the drug. Binding of AmB to lipid monolayers formed with dipalmitoylphosphatidylcholine, pure and containing 40 mol% cholesterol or ergosterol, the sterols of human and fungi respectively, has been examined by means of Fluorescence Lifetime Imaging Microscopy. AmB emits fluorescence with the characteristic lifetimes dependent on actual molecular organization: τM2 ≤ 10 ps and τM1 = 0.35 ns in the monomeric state, the emission from the S2 and the S1 states respectively and τD = 14 ns and τA = 3.5 ns in the form of a dimer and associated dimers respectively. Analysis of the Langmuir-Blodgett films reveals that AmB binds to the lipid membranes and to the cholesterol-containing lipid membranes preferentially in the form of associated dimers. The same form of AmB appears in the membranes containing ergosterol but additionally the monomers and dimers of the drug. can be observed, which can severely affect molecular organization of the lipid membrane. The results are discussed in terms of selectivity of AmB towards the ergosterol-containing biomembranes of fungi.

Original languageEnglish
Pages (from-to)95-101
Number of pages7
JournalBiophysical Chemistry
Volume143
Issue number1-2
DOIs
StatePublished - 1 Jul 2009

Keywords

  • Amphotericin B
  • Biomembranes
  • FLIM
  • Lipid monolayer
  • Polyene antibiotics

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