(721d) Mixed Poly(ethylene glycol) and Poly(sulfobetaine) Brushes to Control Protein Adsorption and Denaturation on Biomaterial Surfaces

Polymer brushes have received considerable attention as coatings to improve the biocompatibility of materials in physiological environments or in contact with proteins for applications including biomaterials for tissue engineering and drug delivery, medical devices, and biosensors. Despite a widespread interest in applications of polymer brushes, a mechanistic understanding of the connection between brush properties and non-specific protein adsorption and denaturation remains elusive. We investigated the effect of grafting density of poly(ethylene glycol) (PEG) brushes on the interactions of the brush with fibronectin (FN) using high-throughput single-molecule tracking methods, which directly measure protein adsorption, diffusion, and unfolding within the brush. We observed that as grafting density increased, the rate of FN adsorption decreased; however, surface-adsorbed FN unfolded more readily and unfolded molecules were retained on the surface for longer residence times relative to folded molecules. While PEG brushes overall exhibited non-fouling properties, they did not prevent protein adsorption completely at the molecular level and, more interestingly, did not preserve the native conformation of protein molecules. Based on these results, we are currently investigating mixed polymer brushes containing PEG and poly(sulfobetaine), a zwitterionic polymer. We hypothesize that the inclusion of poly(sulfobetaine) will mediate the retention of unfolded molecules on PEG brushes by altering the local hydration within the brush. To test this hypothesis, mixed PEG/ poly(sulfobetaine) brushes have been prepared with varying ratios of PEG-to-poly(sulfobetaine), which have been characterized by water contact angle and FTIR-ATR. The adsorption of FN and retention of unfolded FN as a function of the PEG-to-poly(sulfobetaine) has been characterized in analogous single-molecule experiments as in the case of pure PEG. Our studies will provide new insights into the rational design of polymer brushes to improve their performance in biological environments as well as control cellular responses to non-specifically adsorbed protein in the physiological milieu.