Ratiometric control for differentiation of cell populations endowed with synthetic toggle switches
This work addresses a control problem for synthetic biologists managing cell population ratios in microfluidic platforms, but the results are only in-silico and incremental.
The paper tackles the problem of regulating the ratio of two cell populations using external control inputs, assuming cells have a bistable memory mechanism. Three control strategies are proposed and validated in-silico with stochastic simulations.
We consider the problem of regulating by means of external control inputs the ratio of two cell populations. Specifically, we assume that these two cellular populations are composed of cells belonging to the same strain which embeds some bistable memory mechanism, e.g. a genetic toggle switch, allowing them to switch role from one population to another in response to some inputs. We present three control strategies to regulate the populations' ratio to arbitrary desired values which take also into account realistic physical and technological constraints occurring in experimental microfluidic platforms. The designed controllers are then validated in-silico using stochastic agent-based simulations.