A comprehensive reduced model of the mammalian cell cycle

The cellular division cycle is an essential process to ensure healthy tissue homeostasis, which can, due to its periodicity, be interpreted as a biological oscillator. This work focuses on identifying the main mechanisms underlying cell cycle rhythms in mammals and propose a mathematical model to describe them. The model is based on post-translational modifications of cyclin B-cdk1, also called mitosis promoting factor (MPF), known to be the essential protein of the mammalian cell cycle, as well as in its degradation by the APC:cdc20 complex. The final result is a two variable reduced model of the mammalian cell cycle that is able to reproduce oscillatory behaviors and properties consistent with observations, namely the period being tunable by an external input of growth factor. We calibrate and validate this model and study its behavior in a simple open-loop control configuration, showing that it can exhibit bistability and oscillations. The model presents an advantage to work with due to its low variable and parameter size.