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Balancing Cell Populations Endowed with a Synthetic Toggle Switch via Adaptive Pulsatile Feedback Control
journal contribution
posted on 2020-03-20, 16:46 authored by Agostino Guarino, Davide Fiore, Davide Salzano, Mario di BernardoThe problem of controlling
cells endowed with a genetic toggle
switch has been recently highlighted as a benchmark problem in synthetic
biology. It has been shown that a carefully selected periodic forcing
can balance a population of such cells in an undifferentiated state.
The effectiveness of these control strategies, however, can be hindered
by the presence of stochastic perturbations and uncertainties typically
observed in biological systems and is therefore not robust. Here,
we propose the use of feedback control strategies to enhance robustness
and performance of the balancing action by selecting in real-time
both the amplitude and the duty-cycle of the pulsatile inputs affecting
the toggle switch behavior. We show, via in silico experiments and realistic agent-based simulations,
the effectiveness of the proposed strategies even in the presence
of uncertainties, stochastic effects, cell growth, and inducer diffusion.
In so doing, we confirm previous observations made in the literature
about coherence of the population when pulsatile forcing inputs are
used, but, contrary to what was proposed in the past, we leverage
feedback control techniques to endow the balancing strategy with unprecedented
robustness and stability properties. We compare via in silico experiments different external control
solutions and show their advantages and limitations from an in vivo implementation viewpoint.