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Hard Limits and Performance Tradeoffs in a Class of Antithetic Integral Feedback Networks

Olsman, Noah and Baetica, Ania-Ariadna and Xiao, Fangzhou and Leong, Yoke Peng and Murray, Richard M. and Doyle, John C. (2019) Hard Limits and Performance Tradeoffs in a Class of Antithetic Integral Feedback Networks. Cell Systems, 9 (1). pp. 49-63. ISSN 2405-4712. doi:10.1016/j.cels.2019.06.001.

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Feedback regulation is pervasive in biology at both the organismal and cellular level. In this article, we explore the properties of a particular biomolecular feedback mechanism called antithetic integral feedback, which can be implemented using the binding of two molecules. Our work develops an analytic framework for understanding the hard limits, performance tradeoffs, and architectural properties of this simple model of biological feedback control. Using tools from control theory, we show that there are simple parametric relationships that determine both the stability and the performance of these systems in terms of speed, robustness, steady-state error, and leakiness. These findings yield a holistic understanding of the behavior of antithetic integral feedback and contribute to a more general theory of biological control systems.

Item Type:Article
Related URLs:
URLURL TypeDescription
Olsman, Noah0000-0002-4351-3880
Baetica, Ania-Ariadna0000-0003-0421-8181
Xiao, Fangzhou0000-0002-5001-5644
Leong, Yoke Peng0000-0001-8560-8856
Murray, Richard M.0000-0002-5785-7481
Doyle, John C.0000-0002-1828-2486
Additional Information:© 2019 Elsevier. Received 21 September 2018, Revised 28 February 2019, Accepted 30 May 2019, Available online 3 July 2019. The authors would like to thank Reed McCardell for providing insight into the synthetic growth circuit, James Anderson for useful discussions of tools for analyzing nonlinear systems, and Hana El-Samad for providing feedback on the manuscript. The project was sponsored by the Defense Advanced Research Projects Agency (agreement HR0011-17-2-0008). The content of the information does not necessarily reflect the position or the policy of the Government, and no official endorsement should be inferred. Author Contributions: Conceptualization and Methodology, NO, AAB, FX, YPL, JCD, and RMM; formal analysis, NO, AAB, FX, and YPL; software, NO, AAB, and YPL; writing, NO, AAB, and FX; supervision and funding, JCD and RMM. The authors declare no competing interests.
Funding AgencyGrant Number
Defense Advanced Research Projects Agency (DARPA)HR0011-17-2-0008
Subject Keywords:Feedback Regulation; Synthetic Biology; Performance Tradeoffs; Antithetic Integral Feedback
Issue or Number:1
Record Number:CaltechAUTHORS:20190708-153642582
Persistent URL:
Official Citation:Noah Olsman, Ania-Ariadna Baetica, Fangzhou Xiao, Yoke Peng Leong, Richard M. Murray, John C. Doyle, Hard Limits and Performance Tradeoffs in a Class of Antithetic Integral Feedback Networks, Cell Systems, Volume 9, Issue 1, 2019, Pages 49-63.e16, ISSN 2405-4712, (
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:96926
Deposited By: George Porter
Deposited On:08 Jul 2019 22:44
Last Modified:16 Nov 2021 17:24

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