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Robust perfect adaptation in bacterial chemotaxis through integral feedback control

Yi, Tau-Mu and Huang, Yun and Simon, Melvin I. and Doyle, John (2000) Robust perfect adaptation in bacterial chemotaxis through integral feedback control. Proceedings of the National Academy of Sciences of the United States of America, 97 (9). pp. 4649-4653. ISSN 0027-8424. PMCID PMC18287.

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Integral feedback control is a basic engineering strategy for ensuring that the output of a system robustly tracks its desired value independent of noise or variations in system parameters. In biological systems, it is common for the response to an extracellular stimulus to return to its prestimulus value even in the continued presence of the signal-a process termed adaptation or desensitization. Barkai, Alon, Surette, and Leibler have provided both theoretical and experimental evidence that the precision of adaptation in bacterial chemotaxis is robust to dramatic changes in the levels and kinetic rate constants of the constituent proteins in this signaling network [Alon. U., Surette, M. G., Barkai. N. & Leibler, S. (1998) Nature (London) 397, 168-171]. Here we propose that the robustness of perfect adaptation is the result of this system possessing the property of integral feedback control. Using techniques from control and dynamical systems theory, we demonstrate that integral control is structurally inherent in the Barkai-Leibler model and identify and characterize the key assumptions of the model. Most importantly, we argue that integral control in some form is necessary for a robust implementation of perfect adaptation. More generally, integral control may underlie the robustness of many homeostatic mechanisms.

Item Type:Article
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URLURL TypeDescription CentralArticle
Doyle, John0000-0002-1828-2486
Additional Information:© 2000 by the National Academy of Sciences. Contributed by Melvin I. Simon, February 7, 2000. We acknowledge valuable discussions with Drs. S. Lall, H. Berg, D. Petrasek, U. Alon, N. Barkai, and S. Leibler. Special thanks to Drs. U. Alon, H. Berg, J. Stock, and P. Iglesias for comments on the manuscript. This work was supported by an Air Force Office of Scientific Research (AFOSR)/DDRE MURI AFS-5X-F496209610471 grant entitled "Uncertainty Management in Complex Systems" and Defense Advanced Research Planning Agency/AFOSR grant AFS-5-F4962098-L0487. T.-M.Y. was supported by a fellowship from the Caltech Initiative in Computational Molecular Biology funded by the Burroughs–Wellcome Foundation. The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. §1734 solely to indicate this fact.
Funding AgencyGrant Number
Air Force Office of Scientific Research (AFOSR)AFS-5X-F496209610471
Air Force Office of Scientific Research (AFOSR)AFS-5-F4962098-L0487
Defense Advanced Research Projects Agency (DARPA)UNSPECIFIED
Burroughs Wellcome FoundationUNSPECIFIED
Subject Keywords:Escherichia-coli, signal transduction, receptor modification, mechanism, systems, model, phosphorylation, methylesterase, sensitivity, excitation
Issue or Number:9
PubMed Central ID:PMC18287
Record Number:CaltechAUTHORS:YITpnas00
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:999
Deposited By: Tony Diaz
Deposited On:23 Nov 2005
Last Modified:02 Oct 2019 22:39

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