Towards infection resistant surfaces: Polymer brush chemistry and peptide structure modulate the potency of antimicrobial peptides

Event Abstract Back to Event Towards infection resistant surfaces: Polymer brush chemistry and peptide structure modulate the potency of antimicrobial peptides Kai Yu1*, Joey Lo2*, Yan Mei1*, Evan Haney3*, Robert Hancock3*, Dirk Lange2* and Jayachandran Kizhakkedathu1* 1 University of British Columbia, Department of Pathology and lab Medicine & Centre for Blood Research, Canada 2 University of British Columbia, Department of Urologic Sciences, Canada 3 University of British Columbia, Department of Microbiology and Immunology, Canada Introduction: Implanted device associated bacterial infection greatly compromises the long-term performance and stability of the implant, and is associated with increased morbidity and mortality[1]. Antibacterial coatings based on immobilizing antimicrobial peptides (AMPs) into the polymer brush provide a robust anti-infection method which can not only prevent bacterial adhesion but also kill the adhered bacteria on the surface and prevent biofilm formation[2]. However, there is limited information available on how brush chemistry and structure contribute to the interaction of conjugated AMPs, and how these parameters influence the overall antimicrobial activity of the AMP conjugated surfaces. Thus, we investigated the influence of polymer brush chemistry and peptide structure on the antimicrobial activity of peptides conjugated to various polymer brush coated surfaces. Materials and Methods: Polymer brushes containing, DMA:N,N-dimethylacrylamide, MPC:2-methacryloyloxyethyl phosphorylcholine, MPDSAH:[3-(methacryloylamido)propyl)dimethyl(3-sulfopropyl)ammonium hydroxide), APMA: N-(3-Aminopropyl)methacrylamide, P(DMA-co-APMA), P(MPC-co-APMA) and P(MPDSAH-co-APMA), were generated on polystyrene nanoparticles (NPs) and titanium substrate by surface initiated atom transfer radical polymerization[3]. Two cathelicidin-derived peptides, E6 (RRWRIVVIRVRRC) or Tet20 (KRWRIRVRVIRKC), were conjugated to the brushes to construct different combinations of AMPs tethered polymer brush coating. The antimicrobial activity of surface tethered AMPs on three polymer brush systems against Gram-positive (S. aureus) and Gram-negative bacteria (E. coli and P. aeruginosa) was determined. Live/Dead BacLight bacterial viability kit was used to determine bacterial cell viability and adhesion on AMP-brush grafted substrate. Result and Discussion: The successful grafting polymer brushes onto the polystyrene NPs and conjugation of peptides were confirmed by FTIR spectra. The antimicrobial activity of tethered AMPs against E. coli was tested as a function of peptide concentration (Figure 1). As shown, E6 and Tet20 were more effective on PDMA brushes in comparison to PMPC or PMPDSAH brushes at similar AMP concentrations demonstrating the influence of polymer brush chemistry. The observed effect was confirmed for other bacterial species with different outer envelopes, specifically the Gram-positive S. aureus and Gram-negative P. aeruginosa. In addition, polymer brush tethered E6 was more active than tethered Tet20 at all peptide concentrations, confirming the importance of peptide sequence on the activity of tethered peptides. The influence of polymer brush chemistry on antimicrobial activity of tethered peptides and their anti-adhesion properties were further validated by using AMP-brush grafted Ti surface. Figure 2 shows the merged fluorescence images of live and dead bacteria on different polymer brush tethered E6 after incubating with S. aureus. The greater intensity of yellow color on E6 tethered PDMA brush indicated that the percentages of dead bacteria on this surface was much higher than that on E6 conjugated PMPC and PMPDSAH brushes. These results were corroborated with changes in peptide secondary structure analyzed by surface specific CD spectroscopy of AMP tethered brushes in presence of biomembranes. Conclusions: Our results show that the brush chemistry is an important parameter that determines the overall antimicrobial activity of surface conjugated AMPs. These results will have important implications in the design of novel infection-resistant coatings utilizing tethered AMP technology with potent antimicrobial and antifouling characteristics. This research was funded by the Canadian Institutes of Health Research (CIHR) and Natural Science and Engineering Research Council (NSERC) of Canada.References:[1] Hetrick EM, Schoenfisch MH. Chem Soc Rev 2006;35:780-789.[2] Gao GZ, Lange D, Hilpert K, Kindrachuk J, Zou YQ, Cheng JTJ, et al. Biomaterials 2011;32:3899-3909.[3] Barbey R, Lavanant L, Paripovic D, Schuwer N, Sugnaux C, Tugulu S, et al. Chem Rev 2009;109:5437-5527. Keywords: Bacteria, Infection, polymer brush, bioactive interface Conference: 10th World Biomaterials Congress, Montréal, Canada, 17 May - 22 May, 2016. Presentation Type: Poster Topic: Interfacial phenomena Citation: Yu K, Lo J, Mei Y, Haney E, Hancock R, Lange D and Kizhakkedathu J (2016). Towards infection resistant surfaces: Polymer brush chemistry and peptide structure modulate the potency of antimicrobial peptides. Front. Bioeng. Biotechnol. Conference Abstract: 10th World Biomaterials Congress. doi: 10.3389/conf.FBIOE.2016.01.01213 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 27 Mar 2016; Published Online: 30 Mar 2016. * Correspondence: Dr. Kai Yu, University of British Columbia, Department of Pathology and lab Medicine & Centre for Blood Research, Vancouver, BC, Canada, Email1 Dr. Joey Lo, University of British Columbia, Department of Urologic Sciences, Vancouver, BC, Canada, jlo@prostatecentre.com Dr. Yan Mei, University of British Columbia, Department of Pathology and lab Medicine & Centre for Blood Research, Vancouver, BC, Canada, yan.mei@ubc.ca Dr. Evan Haney, University of British Columbia, Department of Microbiology and Immunology, Vancouver, BC, Canada, evan@hancocklab.com Dr. Robert Hancock, University of British Columbia, Department of Microbiology and Immunology, Vancouver, BC, Canada, bob@hancocklab.com Dr. Dirk Lange, University of British Columbia, Department of Urologic Sciences, Vancouver, BC, Canada, dirk.lange@ubc.ca Dr. Jayachandran Kizhakkedathu, University of British Columbia, Department of Pathology and lab Medicine & Centre for Blood Research, Vancouver, BC, Canada, jay@pathology.ubc.ca Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Kai Yu Joey Lo Yan Mei Evan Haney Robert Hancock Dirk Lange Jayachandran Kizhakkedathu Google Kai Yu Joey Lo Yan Mei Evan Haney Robert Hancock Dirk Lange Jayachandran Kizhakkedathu Google Scholar Kai Yu Joey Lo Yan Mei Evan Haney Robert Hancock Dirk Lange Jayachandran Kizhakkedathu PubMed Kai Yu Joey Lo Yan Mei Evan Haney Robert Hancock Dirk Lange Jayachandran Kizhakkedathu Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.