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.
Niels Bohr Institute, University of Copenhagen, Blegdamsvej 17, DK-2100 Copenhagen, Denmark. mhjensen@nbi.dk
Mogens H
MH
Jensen
Sandeep
S
Krishna
D021581:Active Transport, Cell Nucleus; D002467:Cell Nucleus / Q000378:metabolism; D004249:DNA Damage; D025461:Feedback, Physiological; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D008954:Models, Biological; D016328:NF-kappa B / Q000378:metabolism; D017711:Nonlinear Dynamics; D013312:Stress, Physiological; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D016159:Tumor Suppressor Protein p53