Sharing resources can lead to monostability in a network of bistable toggle switches

Research output: Contribution to journalArticle

Abstract

The vision of synthetic biology is to engineer complex cellular systems in a modular fashion. Unfortunately, multiple factors hinder such modular design, thus the scalability of rationally engineering synthetic gene circuits. One major barrier emerges due to the limited availability of shared cellular resources, intertwining the behavior of otherwise disconnected components. It was recently demonstrated that these unwanted and pervasive coupling effects can be accurately predicted both in vitro and in vivo. Here, we not only analyze how these effects influence the collective behavior of multiple toggle switches but we also illustrate how to leverage this predominantly disadvantageous coupling. In particular, we prove that by turning on/off a load module, the network of toggle switches can be switched between monostable and multistable modes. Importantly, this can be achieved without any direct regulatory connection among the toggle switches or between the load module and any of the toggle switches, thus presenting a major experimental advantage over relying on traditional regulatory linkages. This idea of exploiting and leveraging resource competition is illustrated through the design of a cellular random number generator.

Original languageEnglish (US)
Article number8467997
JournalIEEE Control Systems Letters
Volume3
Issue number2
DOIs
StatePublished - Apr 2019

Keywords

  • Biomolecular systems
  • Network analysis and control
  • Stability of nonlinear systems

ASJC Scopus subject areas

  • Control and Systems Engineering
  • Control and Optimization

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