Enhancing the Activity of Surface Immobilized Antimicrobial Peptides Using Thiol‐Mediated Tethering to Poly(ethylene glycol)

Abstract

Considering the need for versatile surface coatings that can display multiple bioactive signals and chemistries, the use of more novel surface modification methods is starting to emerge. Thiol‐mediated conjugation of biomolecules is shown to be quite advantageous for such purposes due to the reactivity and chemoselectivity of thiol functional groups. Herein, the immobilization of poly(ethylene glycol) (PEG) and antimicrobial peptides (AMPs) to silica colloidal particles based on thiol‐mediated conjugation techniques, along with an assessment of the antimicrobial potential of the functionalized particles against Pseudomonas aeruginosa and Staphylococcus aureus is investigated. Immobilization of PEG to thiolated Si particles is performed by either a two‐step thiol–ene “photo‐click” reaction or a “one‐pot” thiol–maleimide type conjugation using terminal acrylate or maleimide functional groups, respectively. It is demonstrated that both immobilization methods result in a significant reduction in the number of viable bacterial cells compared to unmodified samples after the designated incubation periods with the PEG‐AMP‐modified colloidal suspensions. These findings provide a promising outlook for the fabrication of multifunctional surfaces based upon the tethering of PEG and AMPs to colloidal particles through thiol‐mediated biocompatible chemistry, which has potential for use as implant coatings or as antibacterial formulations that can be incorporated into wound dressings to prevent or control bacterial infections.

Functionalization of Polydimethylsiloxane with Diazirine-Based Linkers for Covalent Protein Immobilization

“…Biosensors, such as immunosensors and enzyme electrodes, heavily rely on immobilized proteins and are extensively used for medical diagnostics, food analysis, and environmental monitoring . For biomaterials, immobilized biomolecules can be used to regulate cell adhesion, enhance device biocompatibility, and provide antifouling effects, including reducing microbial adhesion, among other applications. − For example, the immobilization of antimicrobial peptides and proteins onto biomaterial surfaces offers various advantages in preventing bacterial adhesion and biofilm-associated infections due to their wide range of activity, high efficacy, and low propensity for developing resistance. − Additionally, various microfluidic devices also require the attachment of proteins for applications in immunoassays, protein microarrays, cell studies, and functionalized devices such as blood oxygenators. , However, challenges still remain in ensuring consistent and stable activity of biomolecules on surfaces while also preventing their denaturation and undesirable interactions with the surface. , Furthermore, in order to obtain the greatest level of sensitivity and specificity in detection and response, a large amount of desired biomolecules need to be immobilized uniformly over the material with outward presentation of the active site . Various methods have been developed to improve biomolecule immobilization on solid surfaces, which can be divided into three categories: physical adsorption, electrostatic interaction, and covalent bonding. , The first two methods are relatively simple to apply; however, their effects are often temporary and reversible due to the dissociation of immobilized molecules from the surface. , Alternatively, covalent tethering with specific functional groups can be used for immobilization, and this binding process is usually irreversible due to the stable nature of the bond.…”