title: Antithetic Integral Feedback Ensures Robust Perfect Adaptation in Noisy Biomolecular Networks.
abstract: The ability to adapt to stimuli is a defining feature of many biological systems and critical to maintaining homeostasis. While it is well appreciated that negative feedback can be used to achieve homeostasis when networks behave deterministically, the effect of noise on their regulatory function is not understood. Here, we combine probability and control theory to develop a theory of biological regulation that explicitly takes into account the noisy nature of biochemical reactions. We introduce tools for the analysis and design of robust homeostatic circuits and propose a new regulation motif, which we call antithetic integral feedback. This motif exploits stochastic noise, allowing it to achieve precise regulation in scenarios where similar deterministic regulation fails. Specifically, antithetic integral feedback preserves the stability of the overall network, steers the population of any regulated species to a desired set point, and adapts perfectly. We suggest that this motif may be prevalent in endogenous biological circuits and useful when creating synthetic circuits.
authors.affiliation: Department of Biosystems Science and Engineering (D-BSSE), ETH-Zürich, Mattenstrasse 26, 4058 Basel, Switzerland.
authors.forename: Corentin
authors.initials: C
authors.lastname: Briat
authors.affiliation: Department of Biosystems Science and Engineering (D-BSSE), ETH-Zürich, Mattenstrasse 26, 4058 Basel, Switzerland.
authors.forename: Ankit
authors.initials: A
authors.lastname: Gupta
authors.affiliation: Department of Biosystems Science and Engineering (D-BSSE), ETH-Zürich, Mattenstrasse 26, 4058 Basel, Switzerland. Electronic address: mustafa.khammash@bsse.ethz.ch.
authors.forename: Mustafa
authors.initials: M
authors.lastname: Khammash
mesh_terms: D005246:Feedback; D053263:Gene Regulatory Networks; D006706:Homeostasis; D008954:Models, Biological