1. Feedback control promotes synchronisation of the cell-cycle across a population of yeast cells
- Author
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Diego di Bernardo, Sara Napolitano, Giansimone Perrino, Francesca Galdi, Mario di Bernardo, Davide Fiore, Antonella La Regina, Perrino, G., Fiore, D., Napolitano, S., Galdi, F., La Regina, A., di Bernardo, M., and di Bernardo, D.
- Subjects
Sequence ,0303 health sciences ,0209 industrial biotechnology ,education.field_of_study ,Computer science ,Microfluidics ,Population ,Phase (waves) ,02 engineering and technology ,Division (mathematics) ,Cell cycle ,Synchronization ,Yeast ,03 medical and health sciences ,020901 industrial engineering & automation ,Control theory ,education ,Reset (computing) ,030304 developmental biology - 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.
- Published
- 2019
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