title: Effect of cholesterol and ergosterol on the antibiotic amphotericin B interactions with dipalmitoylphosphatidylcholine monolayers: X-ray reflectivity study.
abstract: Amphotericin B is a Streptomyces nodosus metabolite and one of the oldest polyene antibiotics used in the treatment of invasive systemic fungal infections. Despite its over 50-year existence in clinical practice and the recognition of amphotericin B as the gold standard in the treatment of serious systemic mycosis, it still remains one of the most toxic pharmaceuticals. Understanding of the processes at the molecular levels and the interactions between amphotericin B with lipid membranes containing sterols should elucidate the mechanisms of the action and toxicity of this widely used antibiotic. In this work, we use X-ray reflectivity to study the structural changes on a molecular scale after amphotericin B incorporation. These changes are accompanied by an increase in monolayer surface pressure which is more pronounced for ergosterol - rather than cholesterol-rich membranes. The data indicate that this difference is not due to the higher affinity of amphotericin B towards ergosterol-containing membranes but is rather due to a ~3Angstrom corrugation of the monolayer. Furthermore, the total quantity of amphotericin B incorporated into lipid monolayers containing cholesterol and ergosterol is the same.
authors.affiliation: Department of Chemistry, University of Life Sciences in Lublin, Akademicka 15, 20-950 Lublin, Poland. Electronic address: daniel_kaminski3@wp.pl.
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Kamiński
authors.affiliation: Department of Biophysics, University of Life Sciences in Lublin, Akademicka 13, 20-950 Lublin, Poland.
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Czernel
authors.affiliation: Institute for Experimental and Applied Physics, University of Kiel, 24098 Kiel, Germany; Ruprecht Haensel Laboratory, University of Kiel, 24098 Kiel, Germany.
authors.forename: Bridget
authors.initials: B
authors.lastname: Murphy
authors.affiliation: Institute for Experimental and Applied Physics, University of Kiel, 24098 Kiel, Germany; Ruprecht Haensel Laboratory, University of Kiel, 24098 Kiel, Germany.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Runge
authors.affiliation: Institute for Experimental and Applied Physics, University of Kiel, 24098 Kiel, Germany; Ruprecht Haensel Laboratory, University of Kiel, 24098 Kiel, Germany.
authors.forename: Olaf M
authors.initials: OM
authors.lastname: Magnussen
authors.affiliation: Department of Cell Biology, Institute of Biology and Biotechnology, Maria Curie-Skłodowska University, 20-033 Lublin, Poland. Electronic address: mariusz.gagos@poczta.umcs.lublin.pl.
authors.forename: Mariusz
authors.initials: M
authors.lastname: Gagoś
keywords: Amphotericin B; Lipid monolayer; Sterol; X-ray diffraction