NF-kappa B oscillations and cell-to-cell variability

Oscillations of the transcription factor NF-kappa B have been observed experimentally both for cell populations by Hoffmann et al. (2002) and for single cells by Nelson et al. (2004). The latter experiments show significant cell-to-cell variability. We use the (stochastic) Gillespie algorithm to study the set of reactions proposed by Hoffmann et al. and variants thereof. The amounts of cellular NF-kappa B and activated kinase IKK are treated as external parameters. We show that intrinsic fluctuations are small in a model with strong transcription, while they are large for weak transcription. Extrinsic noise can be significant: fluctuations in NF-kappa B affect mainly the amplitude of oscillations, whereas fluctuations in activated IKK affect both their amplitude and period. The latter results are in qualitative agreement with the observations of Nelson et al.