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Ultrasensitive molecular controllers for quasi-integral feedback.

Christian Cuba Samaniego1, Elisa Franco2

  • 1Mechanical and Aerospace Engineering, University of California at Los Angeles, Los Angeles, CA 90095, USA.

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|February 4, 2021
PubMed
Summary

We present a modular strategy for designing molecular quasi-integral feedback controllers using ultrasensitive responses and tunable thresholds. This approach, demonstrated by the brink controller, effectively mitigates noise and disturbances in biological systems.

Keywords:
adaptationfeedbackintegral controlmolecular controllersequestrationsynthetic biologyultrasensitivity

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Area of Science:

  • Systems Biology
  • Synthetic Biology
  • Biochemical Engineering

Background:

  • Feedback control is crucial for automated technologies, mitigating variability and noise.
  • Biological feedback loops are known to reduce noise and shape kinetic responses.
  • Designing molecular integral controllers remains a challenge.

Purpose of the Study:

  • To propose a modular strategy for building molecular quasi-integral feedback controllers.
  • To address the need for effective molecular controllers in biological systems.
  • To provide design principles for robust biological feedback mechanisms.

Main Methods:

  • Utilizing an ultrasensitive response to set controller gain and steady-state error.
  • Employing a tunable threshold for the ultrasensitive response to control the system's equilibrium point.
  • Developing a reaction network, the brink controller, combining molecular sequestration and activation/deactivation cycles.

Main Results:

  • The brink controller reaction network satisfies the proposed design principles.
  • Computational models demonstrate potential biological implementations of brink controllers.
  • Example applications of the brink controller are illustrated.

Conclusions:

  • The proposed modular strategy enables the design of molecular quasi-integral feedback controllers.
  • The brink controller offers a novel approach to robust biological feedback control.
  • This work provides a framework for engineering precise biological control systems.