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Hidden complexity in membrane permeabilization behavior of antimicrobial polycations
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SYSNO ASEP 0538960 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Hidden complexity in membrane permeabilization behavior of antimicrobial polycations Author(s) Shi, S. (DE)
Quarta, N. (DE)
Zhang, H. (CN)
Lu, Z. (CN)
Hof, Martin (UFCH-W) RID, ORCID
Šachl, Radek (UFCH-W) RID, ORCID
Liu, R. (CN)
Hoernke, M. (DE)Source Title Physical Chemistry Chemical Physics. - : Royal Society of Chemistry - ISSN 1463-9076
Roč. 23, č. 2 (2021), s. 1475-1488Number of pages 14 s. Language eng - English Country GB - United Kingdom Keywords Stochastic systems ; Microorganisms ; membranes Subject RIV CF - Physical ; Theoretical Chemistry OECD category Physical chemistry R&D Projects GC20-01401J GA ČR - Czech Science Foundation (CSF) GX19-26854X GA ČR - Czech Science Foundation (CSF) Method of publishing Limited access Institutional support UFCH-W - RVO:61388955 UT WOS 000610150200070 EID SCOPUS 85100049494 DOI 10.1039/D0CP05651K Annotation A promising alternative to classical antibiotics are antimicrobial peptides and their synthetic mimics (smAMPs) that supposedly act directly on membranes. For a more successful design of smAMPs, we need to know how the type of interaction with the membrane determines the type of membrane perturbation. How this, in turn, transfers into selectivity and microbial killing activity is largely unknown. Here, we characterize the action of two smAMPs: MM:CO (a copolymer of hydrophobic cyclooctyl subunits and charged β-monomethyl-α-aminomethyl subunits) and the highly charged poly-NM (a homopolymer of α-aminomethyl subunits). By thorough characterization of vesicle leakage experiments, we elucidate complex membrane perturbation behavior in zwitterionic or negatively charged vesicles. Vesicle leakage data does not entirely agree with the growth inhibition of microbes. Our ensemble of advanced membrane permeabilization approaches clarifies these discrepancies. Long cumulative leakage kinetics show that the two smAMPs act either by transient leakage or by rare stochastic leakage events that occur at charge neutralization in the sample. We determine the strengths of individual leakage events induced by the smAMPs in membranes of various compositions. These strengths indicate changes in leakage mechanism over time and concentration range. Thus, our sophisticated analysis of vesicle leakage experiments reveals a fine-tuned flexibility in membrane permeabilization mechanisms. These details are indispensable in judging and designing membrane-active compounds.
Workplace J. Heyrovsky Institute of Physical Chemistry Contact Michaela Knapová, michaela.knapova@jh-inst.cas.cz, Tel.: 266 053 196 Year of Publishing 2022 Electronic address http://hdl.handle.net/11104/0316696
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