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. Author manuscript; available in PMC: 2018 Jan 23.
Published in final edited form as: Integr Biol (Camb). 2017 Jan 23;9(1):6–21. doi: 10.1039/c6ib00178e

Fig. 5. Application of pulsatile stimulation and mathematical modeling in NFkB signaling.

Fig. 5

A. Short pulses of TNF-alpha mimic physiological TNF-alpha release bursts. These pulsed input are controlled for area and shape to determine the fraction of actively responding cells and heterogeneity of the downstream NFkB response. B. Pulsatile input phase-locks/synchronizes the NFkB response. Entrainment facilitated by cell-to-cell variability and stochastic noise results in enhanced amount of mRNA production. C. (i) Stimulation with various TNF-alpha temporal patterns show differential sensitivities of mRNA transcripts. (ii) Genome-wide transcriptome analysis of entrained cells shows that the signals downstream of NFkB may integrate the upstream signals in three distinct ways depending on the rate constants for mRNA degradation, thus brining distinct fate regulations.