Redox-mediated Biomolecular information transfer in single electrogenetic biological cells

Electronic communication in natural systems makes use, inter alia, of molecular transmission, where electron transfer occurs within networks of redox reactions, which play a vital role in many physiological systems. In view of the limited understanding of redox signaling, we developed an approach and an electrochemical-optical lab-on-a-chip to observe cellular responses in localized redox environments. The developed fluidic micro-system uses electrogenetic bacteria in which a cellular response is activated to electrically and chemically induced stimulations. Specifically, controlled environments for the cells are created by using microelectrodes to generate spatiotemporal redox gradients. The in-situ cellular responses at both single-cell and population levels are monitored by optical microscopy. The elicited electrogenetic fluorescence intensities after 210 min in response to electrochemical and chemical activation were 1.3 × 10⁸±0.30 × 10⁸ arbitrary units (A.U.) and 1.2 × 10⁸±0.30 × 10⁸ A.U. per cell population, respectively, and 1.05 ± 0.01 A.U. and 1.05 ± 0.01 A.U. per-cell, respectively. We demonstrated that redox molecules' mass transfer between the electrode and cells - and not the applied electrical field - activated the electrogenetic cells. Specifically, we found an oriented amplified electrogenetic response on the charged electrodes' downstream side, which was determined by the location of the stimulating electrodes and the flow profile. We then focused on the cellular responses and observed distinct subpopulations that were attributed to electrochemical rather than chemical stimulation, with the distance between the cells and the stimulating electrode being the main determinant. These observations provide a comprehensive understanding of the mechanisms by which diffusible redox mediators serve as electron shuttles, imposing context and activating electrogenetic responses.