Dynamical principles of cell-cycle arrest: Reversible, irreversible, and mixed strategies

摘要

Living cells often alternate between proliferating and nonproliferating states as part of individual or collectivenstrategies to adapt to complex and changing environments. To this aim, they have evolved a biochemical regulatorynnetwork enabling them to switch between cell-division cycles (i.e., oscillatory state) and cell-cycle arrests (i.e.,nsteady state) in response to extracellular cues. This can be achieved by means of a variety of bifurcationnmechanisms that potentially give rise to qualitatively distinct cell-cycle arrest properties. In this paper, we studynthe dynamics of a minimal biochemical network model in which a cell-division oscillator and a differentiationnswitch mutually antagonize. We identify the existence of three biologically plausible bifurcation scenariosnorganized around a codimension-four swallowtail-homoclinic singularity. As a result, the model exhibits a broadnrepertoire of cell-cycle arrest properties in terms of reversibility of these arrests, tunability of interdivision time,nand ability to track time-varying signals. This dynamic versatility would explain the diversity of cell-cycle arrestnstrategies developed in different living species and functional contexts.