High-resolution mapping of bifurcations in nonlinear biochemical circuits

Nat Chem. 2016 Aug;8(8):760-7. doi: 10.1038/nchem.2544. Epub 2016 Jun 20.

Abstract

Analog molecular circuits can exploit the nonlinear nature of biochemical reaction networks to compute low-precision outputs with fewer resources than digital circuits. This analog computation is similar to that employed by gene-regulation networks. Although digital systems have a tractable link between structure and function, the nonlinear and continuous nature of analog circuits yields an intricate functional landscape, which makes their design counter-intuitive, their characterization laborious and their analysis delicate. Here, using droplet-based microfluidics, we map with high resolution and dimensionality the bifurcation diagrams of two synthetic, out-of-equilibrium and nonlinear programs: a bistable DNA switch and a predator-prey DNA oscillator. The diagrams delineate where function is optimal, dynamics bifurcates and models fail. Inverse problem solving on these large-scale data sets indicates interference from enzymatic coupling. Additionally, data mining exposes the presence of rare, stochastically bursting oscillators near deterministic bifurcations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biochemical Phenomena
  • Biological Clocks / physiology
  • DNA
  • DNA Replication
  • Gene Regulatory Networks / physiology*
  • Models, Biological
  • Models, Molecular
  • Nanotechnology / methods*
  • Nonlinear Dynamics
  • Synthetic Biology / methods*

Substances

  • DNA