Mechanistic Study of Membrane Disruption by Antimicrobial Methacrylate Random Copolymers by the Single Giant Vesicle Method
Cationic amphiphilic polymers have been a platform to create new antimicrobial materials that act by disrupting bacterial cell membranes. While activity characterization and chemical optimization have been done in numerous studies, there remains a gap in our knowledge on the antimicrobial mechanisms...
| Veröffentlicht in: | Langmuir : the ACS journal of surfaces and colloids. - 1992. - 37(2021), 33 vom: 24. Aug., Seite 9982-9995 |
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| 1. Verfasser: | |
| Weitere Verfasser: | , , , , , |
| Format: | Online-Aufsatz |
| Sprache: | English |
| Veröffentlicht: |
2021
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| Zugriff auf das übergeordnete Werk: | Langmuir : the ACS journal of surfaces and colloids |
| Schlagworte: | Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Anti-Infective Agents Lipid Bilayers Methacrylates Phosphatidylcholines Polymers |
| Zusammenfassung: | Cationic amphiphilic polymers have been a platform to create new antimicrobial materials that act by disrupting bacterial cell membranes. While activity characterization and chemical optimization have been done in numerous studies, there remains a gap in our knowledge on the antimicrobial mechanisms of the polymers, which is needed to connect their chemical structures and biological activities. To that end, we used a single giant unilamellar vesicle (GUV) method to identify the membrane-disrupting mechanism of methacrylate random copolymers. The copolymers consist of random sequences of aminoethyl methacrylate and methyl (MMA) or butyl (BMA) methacrylate, with low molecular weights of 1600-2100 g·mol-1. GUVs consisting of an 8:2 mixture of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine (POPE) and 1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-(1'-rac-glycerol), sodium salt (POPG) and those with only 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) were prepared to mimic the bacterial (Escherichia coli) or mammalian membranes, respectively. The disruption of bacteria and mammalian cell membrane-mimetic lipid bilayers in GUVs reflected the antimicrobial and hemolytic activities of the copolymers, suggesting that the copolymers act by disrupting cell membranes. The copolymer with BMA formed pores in the lipid bilayer, while that with MMA caused GUVs to burst. Therefore, we propose that the mechanism is inherent to the chemical identity or properties of hydrophobic groups. The copolymer with MMA showed characteristic sigmoid curves of the time course of GUV burst. We propose a new kinetic model with a positive feedback loop in the insertion of the polymer chains in the lipid bilayer. The novel finding of alkyl-dependent membrane-disrupting mechanisms will provide a new insight into the role of hydrophobic groups in the optimization strategy for antimicrobial activity and selectivity |
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| Beschreibung: | Date Completed 26.08.2021 Date Revised 26.08.2021 published: Print-Electronic Citation Status MEDLINE |
| ISSN: | 1520-5827 |
| DOI: | 10.1021/acs.langmuir.1c01047 |