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Area of Science:

  • Cellular dynamics
  • Systems biology
  • Molecular biology

Background:

  • Biological processes are influenced by oscillations and noise.
  • The specific effects of both on the transcription factor nuclear factor κB (NF-κB) activity remain unclear.

Purpose of the Study:

  • To investigate how oscillations and noise affect NF-κB activity.
  • To understand the phenomenon of "cellular mode-hopping" observed in NF-κB oscillations.

Main Methods:

  • Experimental observation of NF-κB oscillations entrained by periodic tumor necrosis factor (TNF) inputs.
  • Comparison of stochastic simulations with deterministic simulations of NF-κB dynamics.
  • Analysis of NF-κB behavior within and outside the chaotic regime of parameter space.

Main Results:

  • NF-κB exhibits "cellular mode-hopping" between frequency modes when entrained by periodic TNF inputs.
  • Noise facilitates mode-hopping across all dynamic regimes.
  • Experimental mode-hopping patterns align with noise-induced hopping outside the chaotic regime, differing from chaotic dynamics.

Conclusions:

  • Noise-induced mode-hopping is a key mechanism in NF-κB dynamics.
  • This phenomenon may enable temporal control of gene expression by different NF-κB-dependent genes.
  • Cellular mode-hopping provides a novel perspective on how cells regulate gene expression in response to external stimuli.