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Guidelines for designing the antithetic feedback motif

Baetica, Ania-Ariadna and Leong, Yoke Peng and Murray, Richard M. (2020) Guidelines for designing the antithetic feedback motif. Physical Biology, 17 (5). Art. No. 055002. ISSN 1478-3967. doi:10.1088/1478-3975/ab8454.

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Integral feedback control is commonly used in mechanical and electrical systems to achieve zero steady-state error following an external disturbance. Equivalently, in biological systems, a property known as robust perfect adaptation guarantees robustness to environmental perturbations and return to the pre-disturbance state. Previously, Briat et al. proposed a biomolecular design for integral feedback control (robust perfect adaptation) called the antithetic feedback motif. The antithetic feedback controller uses the sequestration binding reaction of two biochemical species to record the integral of the error between the current and the desired output of the network it controls. The antithetic feedback motif has been successfully built using synthetic components in vivo in Escherichia coli and Saccharomyces cerevisiae cells. However, these previous synthetic implementations of antithetic feedback have not produced perfect integral feedback control due to the degradation and dilution of the two controller species. Furthermore, previous theoretical results have cautioned that integral control can only be achieved under stability conditions that not all antithetic feedback motifs necessarily fulfill. In this paper, we study how to design antithetic feedback motifs that simultaneously achieve good stability and small steady-state error properties, even as the controller species are degraded and diluted. We provide simple tuning guidelines to achieve flexible and practical synthetic biological implementations of antithetic feedback control. We use several tools and metrics from control theory to design antithetic feedback networks, paving the path for the systematic design of synthetic biological controllers.

Item Type:Article
Related URLs:
URLURL TypeDescription
Baetica, Ania-Ariadna0000-0003-0421-8181
Leong, Yoke Peng0000-0001-8560-8856
Murray, Richard M.0000-0002-5785-7481
Additional Information:© 2020 IOP Publishing Ltd. Received 23 December 2019; Accepted 27 March 2020; Accepted Manuscript online 27 March 2020; Published 3 August 2020.
Funding AgencyGrant Number
Defense Advanced Research Projects Agency (DARPA)HR0011-17-2-0008
Issue or Number:5
Record Number:CaltechAUTHORS:20200401-104547968
Persistent URL:
Official Citation:Ania-Ariadna Baetica et al 2020 Phys. Biol. 17 055002; doi: 10.1088/1478-3975/ab8454
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:102237
Deposited By: Tony Diaz
Deposited On:01 Apr 2020 17:54
Last Modified:16 Nov 2021 18:10

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