A minimal spatio-temporal model of the NF-κB signalling pathway exhibits a range of behaviours

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Abstract

In animal cells, the transcription factor NF-κB regulates many stressful, inflammatory, and innate immune responses. Experiments have revealed that, in response to cell stimulation, NF-κB can exhibit oscillatory dynamics where the nature of these dynamics can influence the pattern of NF-κB-dependent gene expression. Oscillations in NF-κB are believed to depend on a negative feedback loop linking NF-κB and one of its downstream products, namely IκBα. This negative feedback loop is enhanced by cell stimulation. However, it also exists in the absence of cell stimulation. Here we propose a minimal spatio-temporal model of the NF-κB signalling pathway, composed of partial differential equations. Through numerical simulations, we find various combinations of behaviours before and during cell stimulation: equilibrium dynamics (rapid convergence to a solution that is everywhere constant) before cell stimulation, followed by oscillatory dynamics during cell stimulation; oscillatory dynamics before and during cell stimulation; oscillatory dynamics before cell stimulation, followed by equilibrium dynamics during cell stimulation; and equilibrium dynamics before and during cell stimulation. In each case, when cell stimulation ceases, the model quickly returns to its pre-stimulation behaviour. All of these different combinations of behaviours occur for similar sets of parameter values. Therefore, our results may help to explain why, in experiments on the NF-κB pathway involving populations of cells, only a certain fraction of the cells exhibit oscillatory dynamics.

Original languageEnglish
Pages (from-to)2363-2388
Number of pages26
JournalBulletin of Mathematical Biology
Volume76
Issue number10
DOIs
Publication statusPublished - 9 Sep 2014
Externally publishedYes

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Keywords

  • NF- κκB
  • Genetic oscillator
  • Spatio-temporal model
  • Negative feedback
  • Gene regulatory network
  • Cancer

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