Stochastic regulation of NF-kappaB pathway

Living cells may be considered noisy or stochastic biochemical reactors. In eukaryotic cells, in which the number of protein or mRNA molecules is relatively large, the stochastic effects may originate in regulation of gene activity or receptors activation. The stochasticity of activator binding and dissociation is amplified by transcription and translation, since target gene activation results in a burst of mRNAs molecules, and each copy of mRNA then serves as a template for numerous protein molecules. Similarly the single receptor activation can be amplified by the transduction cascade. In the present action I expand our model of the NF-kappaB (Nuclear Factor kappa B) regulatory module (Lipniacki et al., 2006. Biophys. J. 90, pp. 725-742) in order to analyze cell activation at low dose of TNF (Tumor Necrosis Factor). The considered regime of activation is important in analysis of cell-to-cell signaling. Ordinary differential equations, used for description of fast reaction channels of processes involving a large number of molecules, are combined with a stochastic switches to account for activity of genes and TNF receptors. The stochasticity in receptor activation and in gene transcription causes simulated cells to exhibit large variability. Moreover none of them behave like an "average" cell.