Effects of Multi-Phase Control Mechanism on Fibroblast Dynamics: A Segmented Mathematical Modeling Approach.

Area of Science:

• Cellular dynamics and mathematical biology
• Quantitative cell biology
• Systems biology

Background:

• Cell size is a critical factor influencing cellular physiology, including growth, division, and overall function.
• Previous models have explored sizer, timer, and adder cell growth strategies.
• Understanding cell cycle control mechanisms is crucial for predicting population dynamics.

Purpose of the Study:

• To develop a mathematical framework for investigating cell cycle control mechanisms in fibroblast populations.
• To analyze how phase-specific control strategies in S and G2 phases, nonlinear growth, and cell death impact population dynamics.
• To explore the interplay between growth, division, and homeostasis in cell populations.

Main Methods:

• Development of a segmented mathematical framework.
• Agent-based stochastic simulations of cell populations.
• Modeling of sizer, timer, and adder strategies with phase-specific controls.
• Incorporation of nonlinear growth dynamics and cell death.

Main Results:

• Steady-state cell size distribution is determined by division kernels and phase-specific controls, showing robustness to cell death.
• A trade-off exists between extrinsic (population-density-dependent) and intrinsic (cell-size-dependent) growth feedbacks.
• Cell-size-dependent regulation acts as a homeostatic mechanism, reducing relative size variability.
• Population recovery is enhanced by retaining large, proliferation-competent cells.

Conclusions:

• Phase-specific cell cycle controls and division kernels are key determinants of cell size distribution.
• Cell-size-dependent regulation provides proportional homeostasis, while population-density-dependent regulation controls cell numbers.
• The findings offer insights into tissue repair and disease progression by elucidating cell growth and division dynamics.