Stability analysis of a multiscale model including cell-cycle dynamics and populations of quiescent and proliferating cells

Abstract

This paper presents a mathematical analysis on our proposed physiologically structured PDE model that incorporates multiscale and nonlinear features. The model accounts for both mutated and healthy populations of quiescent and proliferating cells at the macroscale, as well as the microscale dynamics of cell cycle proteins. A reversible transition between quiescent and proliferating cell populations is assumed. The growth factors generated from the total cell population of proliferating and quiescent cells influence cell cycle dynamics. As feedback from the microscale, Cyclin D/CDK 4-6 protein concentration determines the transition rates between quiescent and proliferating cell populations. Using semigroup and spectral theory, we investigate the well-posedness of the model, derive steady-state solutions, and find sufficient conditions of stability for derived solutions. In the end, we executed numerical simulations to observe the impact of the parameters on the model's nonlinear dynamics.

Keywords

• multiscale model
• proliferation
• quiescence
• cell cycle dynamics
• steady-states
• cancer