System-Level Network Analysis of a Catechol Component for Redox Bioelectronics

Redox is a ubiquitous biological signaling modality that is providing opportunities for bioelectronics. Various experimental studies have demonstrated that catechols offer unique molecular electronic properties for redox-based bioelectronics because catechols can confer redox activity without conductivity. Here, we fabricated a catechol-containing hydrogel film at an electrode surface and characterized this film using dynamic spectroelectrochemical measurements and physics-based modeling (i.e., reaction–diffusion modeling). We show that (i) the flow of electrons through the catechol film involves a redox reaction network; (ii) the redox-state switching of the catechol node is gated by diffusible electron carriers (i.e., mediators) and synchronized to electron transfer at the electrode; and (iii) a physics-based reaction–diffusion model can be abstracted into readily measurable metrics that can be used to characterize the response characteristics of more complex experimental systems (i.e., systems that cannot be described from first principles). Finally, we performed a simple perturbation analysis to illustrate how theory can guide the selection of metrics capable of detecting interactions between the catechol-coated electrode and bio-relevant nodes of a redox interactome (i.e., metrics that are sensitive to redox network topology). Overall, this work provides a unifying framework to understand catechol-based electrode coatings and suggests how theory can guide the selection of metrics for data-driven analysis in emerging applications in redox bioelectronics.