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Feedback control promotes synchronisation of the cell-cycle across a population of yeast cells

Perrino, Giansimone; Fiore, Davide; Napolitano, Sara; Galdi, Francesca; La Regina, Antonella; di Bernardo, Mario; di Bernardo, Diego

 

Abstract

The periodic process of cell replication by division, known as cell-cycle, is a natural phenomenon occurring asynchronously in any cell population. Here, we consider the problem of synchronising cell-cycles across a population of yeast cells grown in a microfluidics device. Cells were engineered to reset their cell-cycle in response to low methionine levels. Automated syringes enable changing methionine levels (control input) in the microfluidics device. However, the control input resets only those cells that are in a specific phase of the cell-cycle (G1 phase), while the others continue to cycle unperturbed. We devised a simplified dynamical model of the cell-cycle, inferred its parameters from experimental data and then designed two control strategies: (i) an open-loop controller based on the application of periodic stimuli; (ii) a closed-loop model predictive controller (MPC) that selects the sequence of control stimuli which maximises a synchronisation index. Both the proposed control strategies were validated in-silico, together with experimental validation of the open-loop strategy.

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