Multi-rhythmicity generated by coupling two cellular rhythms.

Abstract

The cell cycle and the circadian clock represent two major cellular rhythms, which are coupled because the circadian clock governs the synthesis of several proteins of the network that drives the mammalian cell cycle. Analysis of a detailed model for these coupled cellular rhythms previously showed that the cell cycle can be entrained at the circadian period of 24 h, or at a period of 48 h, depending on the autonomous period of the cell cycle and on the coupling strength. We show by means of numerical simulations that multiple stable periodic regimes, i.e. multi-rhythmicity, may originate from the coupling of the two cellular rhythms. In these conditions, the cell cycle can evolve to any one of two (birhythmicity) or three stable periodic regimes (trirhythmicity). When applied at the right phase, transient perturbations of appropriate duration and magnitude can induce the switch between the different oscillatory states. Such switching is characterized by final state sensitivity, which originates from the complex structure of the attraction basins. By providing a novel instance of multi-rhythmicity in a realistic model for the coupling of two major cellular rhythms, the results throw light on the conditions in which multiple stable periodic regimes may coexist in biological systems.