Tunable Hydrogel Substrates for Studying Pathogen-Host Cell Interactions

Extracellular matrix elasticity has been shown to affect a variety of cellular properties. However, the effect it has on pathogen-host cell interaction has yet to be thoroughly evaluated. Furthering our understanding of pathogenic infection mechanisms could be beneficial to the development of vaccinations for poorly understood pathogens as well as new therapies to combat a rapidly growing antibiotic-resistant pathogen population. We evaluated two polymer systems in this study: a polyacrylamide hydrogel system that was functionalized for cell culture and a poly(ethylene glycol)-norbornene hydrogel system that utilizes thiol-ene click chemistry for simple and rapid functionalization and tunability. Our pathogen of interest is Brucella melitensis, a bacteria that affects millions of people worldwide, through livestock death, zoonotic infection, and bioterroristic threat. Since Brucella melitensis primarily targets phagocytes, macrophages were utilized for evaluating the success of the hydrogels in hosting tissue culture. It was determined that the poly(ethylene glycol)-norbornene system had the most success in culturing healthy cells and easily tuning mechanical characteristics. Based on these results, future studies in the Alge Lab will involve seeding macrophages onto poly(ethylene glycol)-norbornene gels of varying elastic moduli and infecting them with Brucella to investigate the influence of extracellular matrix elasticity on Brucella infection rate