Synthetic Electrophysiology: Manipulating and measuring bioelectric pattern formation with light

Electrical signaling in biology is typically associated with transient action potentials. More generally, electrical tissues are reaction-diffusion systems which could support a broader set of pattern-forming phenomena. Constraints on electrophysiological manipulation and measurement in vivo have made it challenging to study new classes of bioelectric patterns.
Here we present a new strategy to study electrophysiological pattern formation by building synthetic bioelectrical tissues from the bottom-up. We engineer electrically inert mammalian cells to express ion channels, optogenetic actuators, and fluorescent voltage indicators in tandem. By combining patterned illumination and all-optical electrophysiology, we study these synthetic bioelectric tissues as excitable media and compare their dynamics rigorously to mathematical predictions.
We use “synthetic electrophysiology” to engineer bioelectrical circuits capable of simple information processing and memory and to map dynamical stability transitions. We also show that tissues of electrically bistable cells can form spatially structured but time-stationary electrical domains which polarize via nucleation-and-growth phase transitions. Signatures of bistability in a stem cell model of myogenesis suggest that bioelectrical phase transitions may play a physiological role during embryonic development.