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Layered Feedback Control Improves Robust Functionality across Heterogeneous Cell Populations

Ren, Xinying and Murray, Richard M. (2020) Layered Feedback Control Improves Robust Functionality across Heterogeneous Cell Populations. . (Unpublished)

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Realizing homeostatic control of metabolites or proteins is one of the key goals of synthetic circuits. However, if control is only implemented internally in individual cells, cell-cell heterogeneity may break the homeostasis on populationlevel since cells do not contribute equally to the production or regulation. New control structures are needed to achieve robust functionality in heterogeneous cell populations. Quorum sensing(QS) serves as a collective mechanism by releasing and sensing small and diffusible signaling molecules for group decision-making. We propose a layered feedback control structure that includes a global controller using quorum sensing and a local controller via internal signal-receptor systems. We demonstrate with modeling and simulation that the global controller drives contributing cells to compensate for disturbances while the local controller governs the fail-mode performance in non-contributing cells. The layered controller can tolerate a higher portion of non-contributing cells or longer generations of mutant cells while maintaining metabolites or proteins level within a small error range, compared with only internal feedback control. We further discuss the potential of such layered structures in robust control of cell population size,population fraction and other population-dependent functions.

Item Type:Report or Paper (Discussion Paper)
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URLURL TypeDescription Paper
Murray, Richard M.0000-0002-5785-7481
Additional Information:The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license. Posted March 25, 2020. The authors would like to thank Fangzhou Xiao for his insightful discussion and Ronghui Zhu for the suggestion on experimental circuit design. The author X. R is supported the Defense Advanced Research Projects Agency (Agreement HR0011-17-2-0008). The content of the information does not necessarily reflect the position or the policy of the Government, and no official endorsement should be inferred.
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Defense Advanced Research Projects Agency (DARPA)HR0011-17-2-0008
Record Number:CaltechAUTHORS:20200327-083242603
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Official Citation:Layered Feedback Control Improves Robust Functionality across Heterogeneous Cell Populations. Xinying Ren, Richard M Murray. bioRxiv 2020.03.24.006528; doi:
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:102138
Deposited By: Tony Diaz
Deposited On:27 Mar 2020 15:50
Last Modified:16 Nov 2021 18:09

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