Highly Branched Polymers with Polymyxin End Groups Responsive to Pseudomonas aeruginosa

Abstract

Polymyxin peptide conjugated to the end groups of highly branched poly(N-isopropyl acrylamide) was shown to bind to a Gram negative bacterium, Pseudomonas aeruginosa . The nonbound polymer had a lower critical solution temperature (LCST) above 60 °C. However, binding caused aggregation, which was disrupted on cooling of the bacteria and polymer mixture. The data indicate that polymer binding of bacteria occurred by interaction of the end groups with lipopolysaccharide and that the binding decreased the LCST to below 37 °C. Cooling then progressed the polymer/bacteria aggregate through a bound LCST into an open polymer coil conformation that was not adhesive to P. aeruginosa .

Analysis using size exclusion chromatography of poly( N -isopropyl acrylamide) using methanol as an eluent

“…This shows that these polymers, which have been shown to be stimuli-responsive to bacteria in solution and to be useful for aggregation of bacteria [23], [37], [38], had broad molar mass distributions and that molar mass distributions changed following modification and purification (ultra-filtration and precipitation).…”

“…However, chain end functionalization affects their solubility in traditional SEC solvents [23], [37], [38]. The advent of a methanol based system means for the first time it will be possible to disclose the molar mass of these materials before and after chain-end modification.…”

“…The advent of a methanol based system means for the first time it will be possible to disclose the molar mass of these materials before and after chain-end modification. Two previously published systems are vancomycin functional polymers for targeting gram positive bacteria [37] and polymyxin functionalized polymers for targeting gram negative bacteria [38]. In this work we have re-examined polymers from these previous studies (see Supporting information) and the molar mass distributions of these materials are shown below in Fig.…”

Highly-branched poly(N-isopropyl acrylamide)s with core–shell morphology below the lower critical solution temperature

“…These results have important implications for the production of stimulus responsive devices because they indicated that the end groups: 1) penetrate to a limited degree into the polymer coil and 2) that only small changes in the solvation of end groups (e.g. 5 binding to receptors) would be required to drive these materials through a phase transition because the solvation of the shell would be dominated by the penetration of the end groups. Penetration of polar end groups (e.g.…”

Towards being genuinely smart: ‘isothermally-responsive’ polymers as versatile, programmable scaffolds for biologically-adaptable materials

“…70,71 pH is an attractive stimulus given the range found throughout the body and in diseased tissues. 70,71 pH is an attractive stimulus given the range found throughout the body and in diseased tissues.…”