The spatial coordination of mitotic entry can be mediated by trigger waves that activate cyclin B-Cdk1 in a cascade. While the kinematic characterization of mitotic waves has been the focus of existing research, less attention has been paid to the fundamental dynamical implications that the bistability of cyclin B-Cdk1 involves. Using the Xenopus cell-free system and numerical simulations, we investigate a dynamical mechanism by which waves enable efficient resource allocation within a cell without compromising its ability to orchestrate synchronous cell-wide processes. Once externally driven, interphase-arrested cell cycle extracts demonstrate the ability to propagate Cdk1 activation signals over millimeters. This observation indicates that neither cyclin synthesis nor cyclin concentration higher than the Cdk1 activation threshold is required for the system to be responsive to the incoming stimuli and to relay signals. While only a local pacemaker region needs to maintain high Cdk1 activity to serve as the wave source, the wave characteristics are largely determined by the medium with lower cyclin content. The basal level of cyclin required to prime the medium is 30% lower than the activation threshold, thus affirming waves as a mechanism that potentially contributes to efficient cellular resource distribution. Numerical modeling shows how the core design of the Xenopus cell cycle oscillator and its bistable nature support wave stability. Collectively, our findings propose trigger waves as a general mechanism that facilitates efficient spatial distribution of regulatory molecules and resources while ensuring the capacity for robust, large-scale signaling responses when required.
Kim et al. (Sun,) studied this question.