title: Dynamical principles of cell-cycle arrest: reversible, irreversible, and mixed strategies.
abstract: Living cells often alternate between proliferating and nonproliferating states as part of individual or collective strategies to adapt to complex and changing environments. To this aim, they have evolved a biochemical regulatory network enabling them to switch between cell-division cycles (i.e., oscillatory state) and cell-cycle arrests (i.e., steady state) in response to extracellular cues. This can be achieved by means of a variety of bifurcation mechanisms that potentially give rise to qualitatively distinct cell-cycle arrest properties. In this paper, we study the dynamics of a minimal biochemical network model in which a cell-division oscillator and a differentiation switch mutually antagonize. We identify the existence of three biologically plausible bifurcation scenarios organized around a codimension-four swallowtail-homoclinic singularity. As a result, the model exhibits a broad repertoire of cell-cycle arrest properties in terms of reversibility of these arrests, tunability of interdivision time, and ability to track time-varying signals. This dynamic versatility would explain the diversity of cell-cycle arrest strategies developed in different living species and functional contexts.
authors.affiliation: Laboratoire de Physique des Lasers, Atomes, et Molécules, Centre National de la Recherche Scientifique, UMR 8523, Université Lille 1, F-59655 Villeneuve d'Ascq, France. benjamin.pfeuty@univ-lille1.fr
authors.forename: Benjamin
authors.initials: B
authors.lastname: Pfeuty
mesh_terms: D059447:Cell Cycle Checkpoints; D008954:Models, Biological; D013997:Time Factors