preprints.org > computer science and mathematics > applied mathematics > doi: 10.20944/preprints202205.0335.v1

Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Version 1 : Received: 23 May 2022 / Approved: 24 May 2022 / Online: 24 May 2022 (11:52:57 CEST)

The process of revitalising quiescent cells in order for them to proliferate plays a pivotal role in the repair of warn out tissues as well as for tissue homeostasis. This process is also crucial in the growth, development and well-being of higher multi-cellular organisms such as mammals. Deregulation of quiescent-proliferation transition is related to many diseases, in particular cancer. Recent studies have revealed that this process is regulated tightly by the Rb−E2F bistable switch mechanism. Based on experimental observations, in this study, we formulate a mathematical model to examine the effect of the growth factor concentration on the proliferation-quiescence transition in human cells. Working with a non-dimensionalised model, we prove positivity, boundedness and uniqueness of solutions. To understand model solution behaviour close to bifurcation points, we carry out bifurcation analysis, which is further verified by use of numerical bifurcation analysis, sensitivity analysis and numerical simulations. Indeed, bifurcation and numerical analysis of the model predicted a transition between stable, bistable and stable states, which are dependent on the growth factor concentration parameter (GF). The derived predictions confirm experimental observations.

Cell cycle; proliferation; quiescence; system of ODEs; bifurcation analysis; numerical bifurcation analysis; sensitivity analysis

Computer Science and Mathematics, Applied Mathematics

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