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.
Feedback control promotes synchronisation of the cell-cycle across a population of yeast cells / Perrino, G.; Fiore, D.; Napolitano, S.; Galdi, F.; La Regina, A.; di Bernardo, M.; di Bernardo, D.. - 2019:(2019), pp. 933-938. (Intervento presentato al convegno 58th IEEE Conference on Decision and Control, CDC 2019 tenutosi a Acropolis Convention Centre, fra nel 2019) [10.1109/CDC40024.2019.9030216].
Feedback control promotes synchronisation of the cell-cycle across a population of yeast cells
Perrino G.;Fiore D.;Napolitano S.;di Bernardo M.
;di Bernardo D.
2019
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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
