Effect of potassium ions at the different concentration on the interaction between AmB and the lipid monolayer containing cholesterol or ergosterol |
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| Institution: | 1. Shaanxi Engineering Research Center of Controllable Neutron Source, School of Science, Xijing University, Xi’an, 710123, China;2. School of Electronic Information Engineering Internet of Things and Big Data Research Center, Xijing University, Xi’an, 710123, China;1. Department of Biochemistry, Pharmacology and Toxicology, University of Environmental and Life Sciences, Wroclaw, Poland;2. Institute of Genetics and Microbiology, University of Wroclaw, Wroclaw, Poland;3. Department of Biophysics, Wroclaw Medical University, Wroclaw, Poland;1. School of Civil, Environmental and Chemical Engineering, RMIT University, GPO Box 2476, Melbourne 3001, Australia;2. Nanometrology Group, National Institute of Standards and Technology, 100 Bureau Drive, Gaithersburg, MD 20899, United States;3. M&H Materials Pty Ltd, PO Box 1033, Elsternwick, Vic 3185, Australia;1. Department of Nuclear Science & Engineering, Nanjing University of Aeronautics and Astronautics, Nanjing, China;2. Jiangsu Key Laboratory of Nuclear Energy Equipment Materials Engineering, Nanjing, China;1. Center for Membrane and Film Technology, Department of Chemical Science and Engineering, Kobe University, 1-1 Rokkodai, Nada, Kobe 657-8501, Japan;2. Center for Membrane and Film Technology, Graduate School of Science, Technology and Innovation, Kobe University, 1-1 Rokkodai, Nada, Kobe 657-8501, Japan;3. Department of Materials Chemistry, Faculty of Engineering, Shinshu University, 4-17-1 Wakasato, Nagano 380-8553, Japan;1. Centro de Investigação de Montanha (CIMO), Instituto Politécnico de Bragança, Campus de Santa Apolónia, 5300-253 Bragança, Portugal;2. Departamento de Ciencias Farmacéuticas, Facultad de Farmacia, CIETUS-IBSAL, Universidad de Salamanca, 37007 Salamanca, Spain;3. Centre Bio R&D Unit, Association BLC3 – Technology and Innovation Campus, Rua Nossa Senhora da Conceição, n2, 3405-155 Oliveira do Hospital, Portugal;4. Nutrition and Bromatology Group, Department of Analytical and Food Chemistry, Faculty of Science, University of Vigo – Ourense Campus, Ourense, Spain;1. Department of Engineering and System Science, National Tsing Hua University, 101, Section 2 Kuang Fu Road, Hsinchu 30013, Taiwan;2. Institute of Nuclear Energy Research, Atomic Energy Council, 100, Wenhua Road, Jiaan Village, Longtan District, Taoyuan 32546, Taiwan;3. Department of Engineering and System Science, National Tsing Hua University, 101, Section 2 Kuang Fu Road, Hsinchu 30013, Taiwan |
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| Abstract: | AmB is an antifungal drug of polyene. Although it is prone to nephrotoxicity, it is still the gold standard in the clinical treatment of fungal infection. Sterol plays a decisive role in the drug activity of AmB. The antifungal activity of AmB depends on ergosterol in fungal membranes, and its toxicity is related to cholesterol in mammalian membranes. At the same time, AmB interacts with biofilms, leading to a significant loss of potassium ions and affecting the transport of potassium ions across membranes. Meanwhile, metal cation may also affect AmB molecules’ aggregation on the membrane. This paper mainly studied the effects of different concentrations of potassium ions on the interactions between AmB and lipid monolayers containing cholesterol or ergosterol and explored the differences in the impact of varying potassium ions on the drug activity of AmB on monolayers rich in these two kinds of sterols. The results show that potassium ions caused the collapse of lipid monolayer and lipid-AmB monolayer to disappear. The limiting molecular area of these monolayers also increased due to potassium ions. The limiting molecular area of the monolayer in the presence of ergosterol has a great difference in the different concentration of potassium ions, which is different from that in the presence of cholesterol. The presence of potassium ions, regardless of the intensity of K+ ions, increased the maximum elastic modulus of the lipid/sterol monolayer with and without AmB. The presence of potassium ions reduced the influence of AmB on the stability of the lipid monolayer containing cholesterol. The impact of AmB on the stability of the lipid monolayer containing ergosterol was related to the concentration of potassium ions. The potassium ions increased the area of the ordered “island” region on the lipid-AmB monolayer containing cholesterol, and the boundary of the microregion produced different degrees of curvature. However, on the lipid/ergosterol monolayer, 5 mM and 10 mM potassium ions made the holes caused by AmB more denser, and the diameter of holes become larger. These results can help to improve the effect of potassium ions on the transmembrane transport of substances affected by AmB. The results will provide a basis for further exploration of the effect mechanism of metal ions on the antifungal activity of polyene drugs. |
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| Keywords: | Potassium ions Polyene drug Antifungal activity Lipid-sterol monolayer AFM |
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