FigsharePub Date : 2020-03-12DOI: 10.1021/acssynbio.9b00464.s003
Agostino Guarino (8604819), Davide Fiore (8604822), Davide Salzano (8604825), Mario di Bernardo (8604828)
{"title":"Balancing Cell Populations Endowed with a SyntheticnToggle Switch <i>via</i> Adaptive Pulsatile Feedback Control","authors":"Agostino Guarino (8604819), Davide Fiore (8604822), Davide Salzano (8604825), Mario di Bernardo (8604828)","doi":"10.1021/acssynbio.9b00464.s003","DOIUrl":"https://doi.org/10.1021/acssynbio.9b00464.s003","url":null,"abstract":"The problem of controllingncells endowed with a genetic togglenswitch has been recently highlighted as a benchmark problem in syntheticnbiology. It has been shown that a carefully selected periodic forcingncan balance a population of such cells in an undifferentiated state.nThe effectiveness of these control strategies, however, can be hinderednby the presence of stochastic perturbations and uncertainties typicallynobserved in biological systems and is therefore not robust. Here,nwe propose the use of feedback control strategies to enhance robustnessnand performance of the balancing action by selecting in real-timenboth the amplitude and the duty-cycle of the pulsatile inputs affectingnthe toggle switch behavior. We show, <i>via</i> <i>in silico</i> experiments and realistic agent-based simulations,nthe effectiveness of the proposed strategies even in the presencenof uncertainties, stochastic effects, cell growth, and inducer diffusion.nIn so doing, we confirm previous observations made in the literaturenabout coherence of the population when pulsatile forcing inputs arenused, but, contrary to what was proposed in the past, we leveragenfeedback control techniques to endow the balancing strategy with unprecedentednrobustness and stability properties. We compare <i>via</i> <i>in silico</i> experiments different external controlnsolutions and show their advantages and limitations from an <i>in vivo</i> implementation viewpoint.","PeriodicalId":521559,"journal":{"name":"Figshare","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147881467","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}