Establishing the Mechanoselective Adhesion of Microorganisms to Biomaterials

University Of Massachusetts Amherst, Amherst MA

Investigators

Abstract

Indwelling medical devices, including catheters, are indispensable tools in modern healthcare. However, over one-quarter of all healthcare-associated infections in the United States are attributed to central line-associated bloodstream infections and catheter-associated urinary tract infections. While hydrogel coatings are typically applied to catheters to improve patient comfort and lower the nonspecific adsorption of proteins and microorganisms, systematic and fundamental studies that reveal why microbes initially adhere to solid surfaces are lacking and could inform the development of biofouling resistant materials. This project supports fundamental research into how mechanical properties paired with the hydrophilicity of polymer gels impacts the initial attachment of microorganisms. In addition to improving the functionality of antifouling polymer coatings, understanding the materials-biology interface can enable the design of a broad range of hydrogel-coated biomedical devices (i.e., catheters, implants, wound dressings, contact lenses). A key component of this NSF-Biomaterials project is its aim to educate, provide research experiences, and mentor a diverse workforce at the emerging interface of materials science and synthetic biology. Numerous new research experiences for undergraduate and graduate students, including engagement efforts aimed at women and underrepresented populations, will result from this activity, including an educational module for high school students called "Bacteria: Natural versus Engineered". The ability to predict how biofilms respond to substrate mechanics is an open question. This activity will establish the native response of Escherichia coli and Staphylococcus aureus to polymer coatings by correlating microbial attachment to a library of materials with varied structure-property relationships and high-throughput transcriptome analysis of the attached cells. By systematically synthesizing polymer gels from (i) hydrophilic poly(ethylene glycol) dimethacrylate, (ii) hydrophobic polymer polydimethylsiloxane, and (iii) tunable copolymer gels, we will identify how biofilm-forming cells sense and respond to the gels' hydrophilicity and stiffness in relevant regimes for biomaterial applications. Notably, we will elucidate genetic targets for biofilm inhibition that control bacterial adhesion and proliferation on our panel of gels by applying synthetic biology approaches and genome-wide libraries for Escherichia coli and Staphylococcus aureus strains to perform quantitative genotype-phenotype mapping for cellular adhesion to mechano-chemically diverse gel materials. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.