ArticleJournal of the Royal Society, Interface2018
Realizing 'integral control' in living cells: how to overcome leaky integration due to dilution?
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 38 papers.
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Who cites it
38 citing papers in PubMed.
- GenAI-Net: A generative AI framework for automated biomolecular network design.Science advances · 2026Article
- Automated Classification of Homeostasis Structure in Input-Output Networks.Bulletin of mathematical biology · 2026Article
- Toward single-cell control: noise-robust perfect adaptation in biomolecular systems.Nature communications · 2025Article
- Emergent eukaryotic directional sensing via receptor degradation and diffusion.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Article
- Multi-Layer Autocatalytic Feedback Enables Integral Control Amidst Resource Competition and Across Scales.ACS synthetic biology · 2025Article
- Temporal Contrastive Learning through implicit non-equilibrium memory.Nature communications · 2025Article
- Multicellular PID control for robust regulation of biological processes.Journal of the Royal Society, Interface · 2025Article
- Engineering Sequestration-Based Biomolecular Classifiers with Shared Resources.ACS synthetic biology · 2024Article
- Anti-windup strategies for biomolecular control systems facilitated by model reduction theory for sequestration networks.Science advances · 2024Article
- A coarse-grained bacterial cell model for resource-aware analysis and design of synthetic gene circuits.Nature communications · 2024Article
- Design patterns of biological cells.BioEssays : news and reviews in molecular, cellular and developmental biology · 2024Review
- 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
- A cybergenetic framework for engineering intein-mediated integral feedback control systems.Nature communications · 2023Article
- Design Principles Underlying Robust Adaptation of Complex Biochemical Networks.Methods in molecular biology (Clifton, N.J.) · 2023Review
- 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
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2 authors.
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Abstract
A major problem in the design of synthetic genetic circuits is robustness to perturbations and uncertainty. Because of this, there have been significant efforts in recent years in finding approaches to implement integral control in genetic circuits. Integral controllers have the unique ability to make the output of a process adapt perfectly to disturbances. However, implementing an integral controller is challenging in living cells. This is because a key aspect of any integral controller is a 'memory' element that stores the accumulation (integral) of the error between the output and its desired set-point. The ability to realize such a memory element in living cells is fundamentally challenged by the fact that all biomolecules dilute as cells grow, resulting in a 'leaky' memory that gradually fades away. As a consequence, the adaptation property is lost. Here, we propose a general principle for designing integral controllers such that the performance is practically unaffected by dilution. In particular, we mathematically prove that if the reactions implementing the integral controller are all much faster than dilution, then the adaptation error due to integration leakiness becomes negligible. We exemplify this design principle with two synthetic genetic circuits aimed at reaching adaptation of gene expression to fluctuations in cellular resources. Our results provide concrete guidance on the biomolecular processes that are most appropriate for implementing integral controllers in living cells.
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