Effectiveness of a surface-bound antimicrobial peptide as a function of tether length

Increasing bacterial resistance due to the overuse of antibiotics has led to an alarming rate of nosocomial infections and a desperate need for novel antimicrobial methods. Infections associated with medical implantation are not only troublesome costing over $250 million per year to treat, but also painful for patients who are forced to suffer lengthy and painful treatments, long-term hospital stays, and even multiple surgeries. Antimicrobial peptides (AMPs) are short, positively-charged peptides found in the innate immune system of many species, and show a wide range of antibacterial activity, including against antibiotic-resistant bacteria. Recently, functionalizing surfaces with ligands such as AMPs has emerged as a technology for combating the spread of infection, particularly during medical implantation. However, few AMPs have reached clinical trial due to a poor understanding of their mechanisms and potential mammalian cell cytotoxicity. We have covalently linked the AMP chrysophsin-1 to a silicon dioxide surface using a flexible spacer molecule to allow lateral mobility for maintaining activity. Using the Quartz Crystal Microbalance with Dissipation (QCM-D), we can monitor the binding of chrysophsin-1 in terms of mass deposition and film rigidity changes on a surface. Determining the effect of linker length on antimicrobial activity will provide a fundamental structure-activity relationship, thus allowing for more rational designs of antibacterial surfaces as well as improving patient outcomes.