Journal article
Hard Limits and Performance Tradeoffs in a Class of Antithetic Integral Feedback Networks
Cell systems, v 9(1), pp 49-63
24 Jul 2019
PMID: 31279505
Featured in Collection : UN Sustainable Development Goals @ Drexel
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.
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•Feedback control is an essential component of biomolecular systems•The design of feedback systems necessarily imposes performance tradeoffs•We use control theory to study an important class of molecular feedback motifs•Our work provides a map between biochemical parameters and circuit performance
While feedback regulation is pervasive at every level of biology, it has proven difficult to design synthetic biomolecular feedback systems that match the performance found in nature. The recently developed antithetic integral feedback motif provides a promising mechanism for the implementation of robust control of molecular processes. Our work applies mathematical tools from control theory to this motif, with the goal of taking steps towards the development of a coherent theoretical framework to guide the design of synthetic feedback networks. We characterize the stability and performance tradeoffs of the network, clarifying the relationship between low-level biomolecular rate parameters and high-level system performance (e.g., speed, robustness, tracking error). While these observations can be taken separately, we highlight that a mathematical result known as Bode’s integral theorem provides a unifying framework for considering the fundamental constraints on feedback control systems.
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Details
- Title
- Hard Limits and Performance Tradeoffs in a Class of Antithetic Integral Feedback Networks
- Creators
- Noah Olsman - Center for Systems BiologyAnia-Ariadna Baetica - California Institute of TechnologyFangzhou Xiao - California Institute of TechnologyYoke Peng Leong - California Institute of TechnologyRichard M. Murray - California Institute of TechnologyJohn C. Doyle - California Institute of Technology
- Publication Details
- Cell systems, v 9(1), pp 49-63
- Publisher
- Elsevier
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Mechanical Engineering and Mechanics
- Web of Science ID
- WOS:000483321900006
- Scopus ID
- 2-s2.0-85069609537
- Other Identifier
- 991021890002804721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology
- Cell Biology