title: Toward Infection-Resistant Surfaces: Achieving High Antimicrobial Peptide Potency by Modulating the Functionality of Polymer Brush and Peptide.
abstract: Bacterial infection associated with indwelling medical devices and implants is a major clinical issue, and the prevention or treatment of such infections is challenging. Antimicrobial coatings offer a significant step toward addressing this important clinical problem. Antimicrobial coatings based on tethered antimicrobial peptides (AMPs) on hydrophilic polymer brushes have been shown to be one of the most promising strategies to avoid bacterial colonization and have demonstrated broad spectrum activity. Optimal combinations of the functionality of the polymer-brush-tethered AMPs are essential to maintaining long-term AMP activity on the surface. However, there is limited knowledge currently available on this topic. Here we report the development of potent antimicrobial coatings on implant surfaces by elucidating the roles of polymer brush chemistry and peptide structure on the overall antimicrobial activity of the coatings. We screened several combinations of polymer brush coatings and AMPs constructed on nanoparticles, titanium surfaces, and quartz slides on their antimicrobial activity and bacterial adhesion against Gram-positive and Gram-negative bacteria. Highly efficient killing of planktonic bacteria by the antimicrobial coatings on nanoparticle surfaces, as well as potent killing of adhered bacteria in the case of coatings on titanium surfaces, was observed. Remarkably, the antimicrobial activity of AMP-conjugated brush coatings demonstrated a clear dependence on the polymer brush chemistry and peptide structure, and optimization of these parameters is critical to achieving infection-resistant surfaces. By analyzing the interaction of polymer-brush-tethered AMPs with model lipid membranes using circular dichroism spectroscopy, we determined that the polymer brush chemistry has an influence on the extent of secondary structure change of tethered peptides before and after interaction with biomembranes. The peptide structure also has an influence on the density of conjugated peptides on polymer brush coatings and the resultant wettability of the coatings, and both of these factors contributed to the antimicrobial activity and bacterial adhesion of the coatings. Overall, this work highlights the importance of optimizing the functionality of the polymer brush to achieve infection-resistant surfaces and presents important insight into the design criteria for the selection of polymers and AMPs toward the development of potent antimicrobial coating on implants.
authors.forename: Kai
authors.initials: K
authors.lastname: Yu
authors.affiliation: Department of Urologic Sciences, University of British Columbia , Vancouver, British Columbia V5Z 1M9, Canada.
authors.forename: Joey C Y
authors.initials: JC
authors.lastname: Lo
authors.forename: Yan
authors.initials: Y
authors.lastname: Mei
authors.affiliation: Department of Microbiology and Immunology and Centre for Microbial Diseases and Immunity Research, University of British Columbia , Vancouver, British Columbia V6T 1Z4, Canada.
authors.forename: Evan F
authors.initials: EF
authors.lastname: Haney
authors.forename: Erika
authors.initials: E
authors.lastname: Siren
authors.forename: Manu Thomas
authors.initials: MT
authors.lastname: Kalathottukaren
authors.affiliation: Department of Microbiology and Immunology and Centre for Microbial Diseases and Immunity Research, University of British Columbia , Vancouver, British Columbia V6T 1Z4, Canada.
authors.forename: Robert E W
authors.initials: RE
authors.lastname: Hancock
authors.affiliation: Department of Urologic Sciences, University of British Columbia , Vancouver, British Columbia V5Z 1M9, Canada.
authors.forename: Dirk
authors.initials: D
authors.lastname: Lange
authors.forename: Jayachandran N
authors.initials: JN
authors.lastname: Kizhakkedathu
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry* / Q000494:pharmacology; D001419:Bacteria / Q000187:drug effects; D020099:Coated Materials, Biocompatible / Q000737:chemistry; D008826:Microbial Sensitivity Tests; D011108:Polymers / Q000737:chemistry* / Q000494:pharmacology; D019736:Prostheses and Implants
chemical_list: D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D020099:Coated Materials, Biocompatible; D011108:Polymers
keywords: antimicrobial activity; antimicrobial peptides; bacterial adhesion; infection-resistant surfaces; polymer brush chemistry; polymer brush coating