ArticleJournal of the Royal Society, Interface2018
Antithetic proportional-integral feedback for reduced variance and improved control performance of stochastic reaction networks.
Article in Journal of the Royal Society, Interface, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed.
- GenAI-Net: A generative AI framework for automated biomolecular network design.Science advances · 2026Article
- Engineering principles in plant metabolism: integrating control, mechanics, and transport under dynamic environments.Plant physiology · 2026Review
- Toward single-cell control: noise-robust perfect adaptation in biomolecular systems.Nature communications · 2025Article
- Article
- Designing biological network motif-based controllers by reverse engineering Hill function-type models from linear models.Journal of the Royal Society, Interface · 2025Article
- Multicellular PID control for robust regulation of biological processes.Journal of the Royal Society, Interface · 2025Article
- Feed-forward loop improves the transient dynamics of an antithetic biological controller.Journal of the Royal Society, Interface · 2025Article
- Anti-windup strategies for biomolecular control systems facilitated by model reduction theory for sequestration networks.Science advances · 2024Article
- Accelerating Diverse Cell-Based Therapies Through Scalable Design.Annual review of chemical and biomolecular engineering · 2024Review
- Design Principles for Biological Adaptation: A Systems and Control-Theoretic Treatment.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Noise properties of adaptation-conferring biochemical control modules.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Structural identifiability of biomolecular controller motifs with and without flow measurements as model output.PLoS computational biology · 2023Article
- Regulation strategies for two-output biomolecular networks.Journal of the Royal Society, Interface · 2023Article
- Bayesian Optimization for Design of Multiscale Biological Circuits.ACS synthetic biology · 2023Article
- A cybergenetic framework for engineering intein-mediated integral feedback control systems.Nature communications · 2023Article
- Robust homeostasis of cellular cholesterol is a consequence of endogenous antithetic integral control.Frontiers in cell and developmental biology · 2023Article
- Frequency spectra and the color of cellular noise.Nature communications · 2022Article
- A genetic mammalian proportional-integral feedback control circuit for robust and precise gene regulation.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- A hierarchy of biomolecular proportional-integral-derivative feedback controllers for robust perfect adaptation and dynamic performance.Nature communications · 2022Article
- Stabilization of antithetic control via molecular buffering.Journal of the Royal Society, Interface · 2022Article
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3 authors.
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No grant is acknowledged in the PubMed record.
Abstract
The ability of a cell to regulate and adapt its internal state in response to unpredictable environmental changes is called homeostasis and this ability is crucial for the cell's survival and proper functioning. Understanding how cells can achieve homeostasis, despite the intrinsic noise or randomness in their dynamics, is fundamentally important for both systems and synthetic biology. In this context, a significant development is the proposed antithetic integral feedback (AIF) motif, which is found in natural systems, and is known to ensure robust perfect adaptation for the mean dynamics of a given molecular species involved in a complex stochastic biomolecular reaction network. From the standpoint of applications, one drawback of this motif is that it often leads to an increased cell-to-cell heterogeneity or variance when compared to a constitutive (i.e. open-loop) control strategy. Our goal in this paper is to show that this performance deterioration can be countered by combining the AIF motif and a negative feedback strategy. Using a tailored moment closure method, we derive approximate expressions for the stationary variance for the controlled network that demonstrate that increasing the strength of the negative feedback can indeed decrease the variance, sometimes even below its constitutive level. Numerical results verify the accuracy of these results and we illustrate them by considering three biomolecular networks with two types of negative feedback strategies. Our computational analysis indicates that there is a trade-off between the speed of the settling-time of the mean trajectories and the stationary variance of the controlled species; i.e. smaller variance is associated with larger settling-time.
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