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However, how the steady states and the stabilities of the gene circuits are affected by host cell growth is not fully understood. Here, we developed a mathematical model for nonlinear growth feedback based on published experimental data. The model analysis predicts that growth feedback could significantly change the qualitative states of the system. Bistability could emerge in a circuit without positive feedback, and high-order multistability (three or more steady states) arises in the self-activation and toggle switch circuits. Our results provide insight into the potential effects of ultrasensitive growth feedback on the emergence of qualitative states in synthetic circuits and the corresponding underlying mechanism.<\/jats:p>","DOI":"10.1371\/journal.pcbi.1010518","type":"journal-article","created":{"date-parts":[[2022,9,16]],"date-time":"2022-09-16T13:58:31Z","timestamp":1663336711000},"page":"e1010518","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":18,"title":["Emergence of qualitative states in synthetic circuits driven by ultrasensitive growth feedback"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4526-8946","authenticated-orcid":true,"given":"Juan Ramon","family":"Melendez-Alvarez","sequence":"first","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5601-2057","authenticated-orcid":true,"given":"Xiao-Jun","family":"Tian","sequence":"additional","affiliation":[]}],"member":"340","published-online":{"date-parts":[[2022,9,16]]},"reference":[{"issue":"5","key":"pcbi.1010518.ref001","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1038\/nmeth.2926","article-title":"Principles of genetic circuit design","volume":"11","author":"JAN Brophy","year":"2014","journal-title":"Nat Methods"},{"issue":"12","key":"pcbi.1010518.ref002","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.1038\/nbt.1591","article-title":"Next-generation synthetic gene networks","volume":"27","author":"TK Lu","year":"2009","journal-title":"Nat Biotechnol"},{"issue":"7067","key":"pcbi.1010518.ref003","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1038\/nature04342","article-title":"Foundations for engineering biology","volume":"438","author":"D. 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