Inducing phase-locking and chaos in cellular oscillators by modulating the driving stimuli

Inflammatory responses in eucaryotic cells are often associated with oscillations in the nuclear-cytoplasmic translocation of the transcription factor NF-kB. In most laboratory realizations, the oscillations are triggered by a cytokine stimulus. We use a mathematical model to show that an oscillatory external stimulus can synchronize the NF-kB oscillations into states where the ratios of the internal to external frequency are close to rational numbers. We predict a response diagram of the TNF-driven NF-kB system which exhibits bands of synchronization known as Arnold tongues. We suggest that when the amplitude of the external stimulus exceeds a certain threshold, chaotic dynamics of the nuclear NF-kB concentration may occur. This behavior seems independent of the shape of the external oscillation and the non-linearities transducing this signal. (C) 2012 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.