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PEG Bottle Brush Copolymers as Antimicrobial Mimics: Role of Entropic Templating in Membrane Lysis

Author:
Garle, Amit L., Budhlall, Bridgette M.
Source:
Langmuir 2019 v.35 no.9 pp. 3372-3382
ISSN:
1520-5827
Subject:
Escherichia coli, Gram-negative bacteria, composite polymers, dyes, encapsulation, erythrocyte membrane, erythrocytes, ethanolamine, moieties, phospholipids, zwitterions
Abstract:
Novel polymers containing quaternary functional groups, with and without (control copolymer) PEG side chains, were synthesized and characterized for their ability to lyse the phospholipid membranes of liposome vesicles. Calcein loaded unilamellar vesicles composed of 1,2-dioleoyl-sn-glycero-3-phosphatidylcholine (DOPC) were used to mimic red-blood cell membranes, and a 80:20 (mol/mol) mixture of 1,2-dioleoyl-sn-glycero-3-phosphatidyl ethanolamine (DOPE) and 1,2-dioleoyl-sn- glycero-3-[phospho-rac-(1-glycerol)] (DOPG) was used to mimic the outer cell-membrane of the gram-negative bacteria, E. coli. For DOPE/DOPG = 80:20 (mol/mol) liposome vesicles, the PEG bottle brush copolymer caused leakage of the encapsulated Calcein dye, whereas the control copolymer did not cause any leakage. Both the bottle brush copolymer and the copolymer without PEG side chains had no effect on the zwitterionic DOPC liposome vesicles indicating that the RBC membrane composition is not disrupted by either copolymer architecture. The PEG bottle brush copolymer did not affect the colloidal size of the DOPE/DOPG = 80:20 (mol/mol) liposome vesicles, but on the addition of Triton-X 100, the vesicles disappeared. This provided evidence that the dye leakage was caused by compromising the integrity of the vesicle membrane by the bottle brush polymer architecture. Such partial disruption was preceded by the entropic templating of lipid membranes by the PEG side chains of the bottle brush copolymer. By careful comparison with non-PEGylated cationic polymers, Quart, the importance of PEG side chains in the membrane disrupting activity of the PEGylated cationic polymer, QPEG, was demonstrated. This finding itself is interesting and can contribute to the expansion of the design of membrane disrupting materials.
Agid:
6323403