Coupling between feedback loops in autoregulatory networks affects bistability range, open-loop gain and switching times

dc.citation.firstpage55003
dc.citation.journalTitlePhysical Biology
dc.citation.volumeNumber9
dc.contributor.authorTiwari, Abhinav
dc.contributor.authorIgoshin, Oleg A.
dc.date.accessioned2013-03-29T20:22:44Z
dc.date.available2014-03-30T05:10:05Z
dc.date.issued2012
dc.description.abstractBiochemical regulatory networks governing diverse cellular processes such as stress-response, differentiation and cell cycle often contain coupled feedback loops. We aim at understanding how features of feedback architecture, such as the number of loops, the sign of the loops and the type of their coupling, affect network dynamical performance. Specifically, we investigate how bistability range, maximum open-loop gain and switching times of a network with transcriptional positive feedback are affected by additive or multiplicative coupling with another positive- or negative-feedback loop. We show that a network's bistability range is positively correlated with its maximum open-loop gain and that both quantities depend on the sign of the feedback loops and the type of feedback coupling. Moreover, we find that the addition of positive feedback could decrease the bistability range if we control the basal level in the signal-response curves of the two systems. Furthermore, the addition of negative feedback has the capacity to increase the bistability range if its dissociation constant is much lower than that of the positive feedback. We also find that the addition of a positive feedback to a bistable network increases the robustness of its bistability range, whereas the addition of a negative feedback decreases it. Finally, we show that the switching time for a transition from a high to a low steady state increases with the effective fold change in gene regulation. In summary, we show that the effect of coupled feedback loops on the bistability range and switching times depends on the underlying mechanistic details.
dc.embargo.terms1 year
dc.identifier.citationTiwari, Abhinav and Igoshin, Oleg A.. "Coupling between feedback loops in autoregulatory networks affects bistability range, open-loop gain and switching times." <i>Physical Biology,</i> 9, (2012) IOP Publishing: 55003. http://dx.doi.org/10.1088/1478-3975/9/5/055003.
dc.identifier.doihttp://dx.doi.org/10.1088/1478-3975/9/5/055003
dc.identifier.urihttps://hdl.handle.net/1911/70867
dc.language.isoeng
dc.publisherIOP Publishing
dc.rightsArticle is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
dc.titleCoupling between feedback loops in autoregulatory networks affects bistability range, open-loop gain and switching times
dc.typeJournal article
dc.type.dcmiText
dc.type.publicationpublisher version
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