Coupling of the cell cycle and metabolism in yeast cell-cycle-related oscillations via resource criticality and checkpoint gating

Abstract

We investigate the possibility that slow metabolic, cell-cycle-related oscillations in yeast and associated temporal clustering of cells within the cell cycle could be due to an interplay between near-critical metabolism and cell cycle checkpoints. We construct a dynamical model of the cell cycles of a large culture of cells that incorporates checkpoint gating and metabolic mode switching that are triggered by resource thresholds. We investigate the model analytically and prove that there exist open sets of parameter values for which the model possesses stable periodic solutions that exhibit metabolic oscillations with cell cycle clustering. Simulations of the model give evidence that such solutions exist for large sets of parameter values. This demonstrates that checkpoint gating coupled with critical resources can be a robust mechanism for producing the phenomena observed in experiments. ARTICLE HISTORY

Universality of stable multi-cluster periodic solutions in a population model of the cell cycle with negative feedback

“…A checkpoint, a phase of the cell cycle where progress may be arrested until sufficient conditions are satisfied [13], is a natural candidate for a responsive phase (R in our model) with negative feedback. This particular mechanism was modelled and studied in [22].…”