Towards Infection Resistant Surfaces: Achieving High Antimicrobial Peptide Potency by Modulating the Functionality of Polymer Brush and Peptide.

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 to address 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. The optimal combinations of the functionality of polymer brush and tethered AMPs are essential to maintain 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 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 coating demonstrated a clear dependence on the polymer brush chemistry and peptide structure, and optimization of these parameters is critical to achieve infection resistant surfaces. By analyzing the interaction of polymer brush tethered AMPs with model lipid membranes using circular dichroism spectroscopy, we determined that polymer brush chemistry has 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 these factors contributed to the antimicrobial activity and bacterial adhesion of the coatings. Overall, this work highlights the importance of optimizing the functionality of polymer brush to achieve infection resistant surfaces and presents important insight into the design criteria for the selection of polymers and AMPs towards the development of potent antimicrobial coating on implants.