Synthetic electrophysiology: optically controlled oscillators in an engineered bioelectric tissue

Multicellular electrical dynamics underlie crucial physiological functions, but the complexity of natural bioelectricity can obscure the relation of individual components (proteins, cells) to emergent system-level dynamics. Here we introduce optopatch-spiking HEK(OS-HEK) tissue, a minimal synthetic bioelectric tissue with 4 transgenic components that supports optical initiation of propagating electrical waves as well direct optical voltage readout. In conjunction with a home-built inverted microscope capable of patterned illumination, we use this tissue to probe the biophysical attributes of this excitable bioelectric medium, including dispersion relations, curvature-dependent wavefront propagation, electrotonic coupling, and effects of boundaries. We then used chemical patterning to define cellular circuits that support controllable oscillations and which retain memory for more than 2 hours (corresponding to 10$^{\mathrm{4}}$ oscillations), constituting a substrate for binary bioelectric data storage. Finally, we use optical patterning of boundary conditions in a physically homogeneous tissue to design dynamically reconfigurable oscillators.