A Model for the Proliferation–Quiescence Transition in Human Cells

Abstract

The process of revitalising quiescent cells in order for them to proliferate plays a pivotal role in the repair of worn-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 proliferation-quiescence transition is related to many diseases, such as cancer. Recent studies have revealed that this proliferation–quiescence 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 the positivity, boundedness and uniqueness of solutions. To understand model solution behaviour close to bifurcation points, we carry out bifurcation analysis, which is further illustrated by the use of numerical bifurcation analysis, sensitivity analysis and numerical simulations. Indeed, bifurcation and numerical analysis of the model predicted a transition between bistable and stable states, which are dependent on the growth factor concentration parameter (GF). The derived predictions confirm experimental observations.