Stabilisation of Antithetic Control via Molecular Buffering

Edward Hancock, Diego A Oyarzún

Research output: Contribution to journalArticlepeer-review

Abstract

A key goal in synthetic biology is the construction of molecular circuits that robustly adapt to perturbations. Although many natural systems display perfect adaptation, whereby stationary molecular concentrations are insensitive to perturbations, its de novo engineering has proven elusive. The discovery of the antithetic control motif was a significant step toward a universal mechanism for engineering perfect adaptation. Antithetic control provides perfect adaptation in a wide range of systems, but it can lead to oscillatory dynamics due to loss of stability, and moreover, it can lose perfect adaptation in fast growing cultures. Here, we introduce an extended antithetic control motif that resolves these limitations. We show that molecular buffering, a widely conserved mechanism for homeostatic control in nature, stabilises oscillations and allows for near-perfect adaptation during rapid growth. We study multiple buffering topologies and compare their performance in terms of their stability and adaptation properties. We illustrate the benefits of our proposed strategy in exemplar models for biofuel production and growth rate control in bacterial cultures. Our results provide an improved circuit for robust control of biomolecular systems.
Original languageEnglish
Article number20210762
Number of pages11
JournalJournal of The Royal Society Interface
Volume19
Issue number188
DOIs
Publication statusPublished - 9 Mar 2022

Keywords

  • buffering
  • antithetic control
  • feedback
  • biomolecular control

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