In Vivo Feedback Control of an Antithetic Molecular-Titration Motif in Escherichia coli Using Microfluidics

ACS Synth Biol. 2020 Oct 16;9(10):2617-2624. doi: 10.1021/acssynbio.0c00105. Epub 2020 Oct 2.

Abstract

We study both in silico and in vivo the real-time feedback control of a molecular titration motif that has been earmarked as a fundamental component of antithetic and multicellular feedback control schemes in E. coli. We show that an external feedback control strategy can successfully regulate the average fluorescence output of a bacterial cell population to a desired constant level in real-time. We also provide in silico evidence that the same strategy can be used to track a time-varying reference signal where the set-point is switched to a different value halfway through the experiment. We use the experimental data to refine and parametrize an in silico model of the motif that can be used as an error computation module in future embedded or multicellular control experiments.

Keywords: external control loop; in vivo feedback control; microfluidics; synthetic biology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 4-Butyrolactone / analogs & derivatives
  • 4-Butyrolactone / metabolism
  • Cell Communication / physiology
  • Computer Simulation
  • Escherichia coli / genetics*
  • Escherichia coli / metabolism*
  • Feedback, Physiological*
  • Gene Expression Regulation, Bacterial
  • Gene Regulatory Networks
  • Green Fluorescent Proteins / metabolism
  • Isopropyl Thiogalactoside / metabolism
  • Kinetics
  • Microfluidics / methods*
  • Microscopy, Fluorescence
  • Models, Biological

Substances

  • homoserine lactone
  • Green Fluorescent Proteins
  • Isopropyl Thiogalactoside
  • 4-Butyrolactone