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

Noah Olsman; Ania-Ariadna Baetica; Fangzhou Xiao; Yoke Peng Leong; Richard M Murray; John C Doyle

doi:10.1016/j.cels.2019.06.001

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

Cell Syst. 2019 Jul 24;9(1):49-63.e16. doi: 10.1016/j.cels.2019.06.001. Epub 2019 Jul 3.

Authors

Noah Olsman¹, Ania-Ariadna Baetica², Fangzhou Xiao³, Yoke Peng Leong⁴, Richard M Murray⁵, John C Doyle⁵

Affiliations

¹ Department of Control and Dynamical Systems, California Institute of Technology, 1200 E, Pasadena, CA 91125, USA; Department of Systems Biology, Harvard Medical School, Boston, MA 02215, USA. Electronic address: noah_olsman@hms.harvard.edu.
² Department of Control and Dynamical Systems, California Institute of Technology, 1200 E, Pasadena, CA 91125, USA; Department of Biochemistry and Biophysics, University of California, San Francisco, Box 2542, San Francisco, CA 94158, USA.
³ Division of Biology and Biological Engineering, California Institute of Technology, 1200 E, Pasadena, CA 91125, USA.
⁴ Department of Control and Dynamical Systems, California Institute of Technology, 1200 E, Pasadena, CA 91125, USA.
⁵ Department of Control and Dynamical Systems, California Institute of Technology, 1200 E, Pasadena, CA 91125, USA; Division of Biology and Biological Engineering, California Institute of Technology, 1200 E, Pasadena, CA 91125, USA.

PMID: 31279505
DOI: 10.1016/j.cels.2019.06.001

Abstract

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.

Keywords: Antithetic Integral Feedback; Feedback Regulation; Performance Tradeoffs; Synthetic Biology.

Publication types

Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Animals
Feedback, Physiological*
Homeostasis
Humans
Models, Biological*
Synthetic Biology
Systems Biology / methods*