title: Noise Induces Hopping between NF-κB Entrainment Modes.
abstract: Oscillations and noise drive many processes in biology, but how both affect the activity of the transcription factor nuclear factor κB (NF-κB) is not understood. Here, we observe that when NF-κB oscillations are entrained by periodic tumor necrosis factor (TNF) inputs in experiments, NF-κB exhibits jumps between frequency modes, a phenomenon we call "cellular mode-hopping." By comparing stochastic simulations of NF-κB oscillations to deterministic simulations conducted inside and outside the chaotic regime of parameter space, we show that noise facilitates mode-hopping in all regimes. However, when the deterministic system is driven by chaotic dynamics, hops between modes are erratic and short-lived, whereas in experiments, the system spends several periods in one entrainment mode before hopping and rarely visits more than two modes. The experimental behavior matches our simulations of noise-induced mode-hopping outside the chaotic regime. We suggest that mode-hopping is a mechanism by which different NF-κB-dependent genes under frequency control can be expressed at different times.
authors.affiliation: Niels Bohr Institute, University of Copenhagen, 2100 Copenhagen, Denmark.
authors.forename: Mathias
authors.initials: M
authors.lastname: Heltberg
authors.affiliation: Department of Biosystems Science and Engineering, ETH Zürich, 8092 Zürich, Switzerland.
authors.forename: Ryan A
authors.initials: RA
authors.lastname: Kellogg
authors.affiliation: Niels Bohr Institute, University of Copenhagen, 2100 Copenhagen, Denmark; Simons Center for the Study of Living Machines, National Center for Biological Sciences, Bangalore 560065, Karnataka, India.
authors.forename: Sandeep
authors.initials: S
authors.lastname: Krishna
authors.affiliation: Department of Biosystems Science and Engineering, ETH Zürich, 8092 Zürich, Switzerland; Institute for Molecular Engineering, University of Chicago, Chicago, IL 60637, USA; Institute for Genomics and Systems Biology, University of Chicago, Chicago, IL 60637, USA. Electronic address: tays@uchicago.edu.
authors.forename: Savaş
authors.initials: S
authors.lastname: Tay
authors.affiliation: Niels Bohr Institute, University of Copenhagen, 2100 Copenhagen, Denmark. Electronic address: mhjensen@nbi.ku.dk.
authors.forename: Mogens H
authors.initials: MH
authors.lastname: Jensen