Spatiotemporal dynamics of distributed synthetic genetic circuits

• We propose and study distributed gene networks, a toggle-switch and an oscillator.
• The networks consist of two interacting subunits shared between two cell strains.
• The toggle-switch cell culture is controllable with external stimuli.
• The oscillatory cell culture gets synchronized by intercellular signaling.
• We discuss potential biosensing properties of the proposed circuits.

We propose and study models of two distributed synthetic gene circuits, toggle-switch and oscillator, each split between two cell strains and coupled via quorum-sensing signals. The distributed toggle switch relies on mutual repression of the two strains, and oscillator is comprised of two strains, one of which acts as an activator for another that in turn acts as a repressor. Distributed toggle switch can exhibit mobile fronts, switching the system from the weaker to the stronger spatially homogeneous state. The circuit can also act as a biosensor, with the switching front dynamics determined by the properties of an external signal. Distributed oscillator system displays another biosensor functionality: oscillations emerge once a small amount of one cell strain appears amid the other, present in abundance. Distribution of synthetic gene circuits among multiple strains allows one to reduce crosstalk among different parts of the overall system and also decrease the energetic burden of the synthetic circuit per cell, which may allow for enhanced functionality and viability of engineered cells.