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Related Experiment Videos

NF-kappaB oscillations and cell-to-cell variability.

F Hayot1, C Jayaprakash

  • 1Department of Physics, Ohio State University, Columbus, OH 43210-1106, USA. hayot@mps.ohio-state.edu

Journal of Theoretical Biology
|December 13, 2005
PubMed
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Nuclear factor-kappaB (NF-kappaB) oscillations are influenced by intrinsic and extrinsic cellular fluctuations. Intrinsic fluctuations are small with strong transcription but can be large with weak transcription. Extrinsic fluctuations in NF-kappaB or IKK impact oscillation amplitude and period.

Area of Science:

  • Cellular and Molecular Biology
  • Systems Biology
  • Biophysics

Background:

  • Nuclear factor-kappaB (NF-kappaB) signaling exhibits oscillations upon cellular stimulation, driven by a negative feedback loop involving IkappaB.
  • These oscillations have been observed in both cell populations and single cells, highlighting their biological significance.

Purpose of the Study:

  • To investigate the sources of cell-to-cell variability in NF-kappaB oscillations using a computational model.
  • To analyze the impact of intrinsic and extrinsic fluctuations on the dynamics of NF-kappaB oscillations.

Main Methods:

  • Utilized Gillespie's algorithm to simulate a simplified IkappaB-NF-kappaB signaling model.
  • Varied cellular NF-kappaB and activated IKK amounts as external parameters to assess fluctuation effects.

Related Experiment Videos

  • Examined models with both strong and weak transcriptional regulation.

    • Main Results:

    • Intrinsic fluctuations were found to be small in models with strong transcription, regardless of transcriptional regulation type (linear or quadratic).
    • Intrinsic fluctuations can become significant in models with weak transcription.
    • Extrinsic fluctuations in initial cellular NF-kappaB primarily affected oscillation amplitude, while activated IKK fluctuations impacted both amplitude and period.

    Conclusions:

    • Cell-to-cell variability in NF-kappaB oscillations is significantly influenced by both intrinsic and extrinsic factors.
    • The model's predictions align with experimental observations of considerable cell-to-cell variability in NF-kappaB signaling dynamics.