title: Geometric analysis of the Goldbeter minimal model for the embryonic cell cycle.
abstract: A minimal model describing the embryonic cell division cycle at the molecular level in eukaryotes is analyzed mathematically. It is known from numerical simulations that the corresponding three-dimensional system of ODEs has periodic solutions in certain parameter regimes. We prove the existence of a stable limit cycle and provide a detailed description on how the limit cycle is generated. The limit cycle corresponds to a relaxation oscillation of an auxiliary system, which is singularly perturbed and has the same orbits as the original model. The singular perturbation character of the auxiliary problem is caused by the occurrence of small Michaelis constants in the model. Essential pieces of the limit cycle of the auxiliary problem consist of segments of slow motion close to several branches of a two dimensional critical manifold which are connected by fast jumps. In addition, a new phenomenon of exchange of stability occurs at lines, where the branches of the two-dimensional critical manifold intersect. This novel type of relaxation oscillations is studied by combining standard results from geometric singular perturbation with several suitable blow-up transformations.
authors.affiliation: Max Planck Institute for Mathematics in the Sciences, Inselstraße 22, 04103, Leipzig, Germany. ilona.kosiuk@mis.mpg.de.
authors.forename: Ilona
authors.initials: I
authors.lastname: Kosiuk
authors.affiliation: Institute for Analysis and Scientific Computing, Technische Universität Wien, Wiedner Hauptstraße 8-10, 1040, Vienna, Austria. szmolyan@tuwien.ac.at.
authors.forename: Peter
authors.initials: P
authors.lastname: Szmolyan
mesh_terms: D000818:Animals; D016203:CDC2 Protein Kinase / Q000378:metabolism; D002453:Cell Cycle / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D003198:Computer Simulation; D016213:Cyclins / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D055641:Mathematical Concepts; D008954:Models, Biological; D017711:Nonlinear Dynamics
chemical_list: D016213:Cyclins; D016203:CDC2 Protein Kinase
keywords: Blow-up method; Cell cycle; Enzyme kinetics; Geometric singular perturbation theory; Mitotic oscillator; Relaxation oscillations