Alternating oscillations and chaos in a model of two coupled biochemical oscillators driving successive phases of the cell cycle.

The animal cell cycle is controlled by the periodic variation of two cyclin-dependent protein kinases, cdk1 and cdk2, which govern the entry into the M (mitosis) and S (DNA replication) phases, respectively. The ordered progression between these phases is achieved thanks to the existence of checkpoint mechanisms based on mutual inhibition of these processes. Here we study a simple theoretical model for oscillations in cdk1 and cdk2 activity, involving mutual inhibition of the two oscillators. Each minimal oscillator is described by a three-variable cascade involving a cdk, together with the associated cyclin and cyclin-degrading enzyme. The dynamics of this skeleton model of coupled oscillators is determined as a function of the strength of their mutual inhibition. The most common mode of dynamic behavior, obtained under conditions of strong mutual inhibition, is that of alternating oscillations in cdk1 and cdk2, which correspond to the physiological situation of the ordered recurrence of the M and S phases. In addition, for weaker inhibition we obtain evidence for a variety of dynamic phenomena such as complex periodic oscillations, chaos, and the coexistence between multiple periodic or chaotic attractors. We discuss the conditions of occurrence of these various modes of oscillatory behavior, as well as their possible physiological significance.