Effects of multi-phase control mechanism on fibroblast dynamics: A segmented mathematical modeling approach

TL;DR

This study introduces a segmented mathematical model to analyze how multi-phase control mechanisms influence fibroblast cell size, growth, and population dynamics, revealing robustness and trade-offs in size regulation strategies.

Contribution

The paper extends previous models by incorporating phase-specific control schemes and nonlinear growth dynamics, providing new insights into cell size regulation and population homeostasis.

Findings

Steady-state size distribution is mainly influenced by division kernels and control strategies.

Size regulation mechanisms are robust to different cell death modes.

Population recovery is faster with retention of large, proliferative cells.

Abstract

Cell size is a fundamental determinant of cellular physiology, influencing processes such as growth, division, and function. In this study, we develop a segmented mathematical framework to investigate how different control mechanisms operating across multiple phases of the cell cycle affect fibroblast population dynamics. Building on our previous work modeling sizer, timer, and adder strategies, we extend the analysis by introducing phase-specific control schemes in the S and G2 phases, incorporating nonlinear growth dynamics and cell death. Using agent-based stochastic simulations, we examine how these mechanisms shape steady-state size distributions and respond to parameter variations. Our results reveal that the steady-state cell size distribution is primarily governed by division kernels and phase-specific control strategies, and appears remarkably robust to cell death modalities. We identify a fundamental trade-off between extrinsic and intrinsic growth feedbacks: while population-density-dependent regulation tightly limits total cell numbers, cell-size-dependent regulation acts as a proportional homeostatic mechanism, suppressing relative size variability. Furthermore, we demonstrate that population recovery is accelerated by the retention of proliferation-competent large cells. This study provides biologically relevant insights into the complex interplay between growth, division, and homeostasis, with implications for understanding tissue repair and disease progression.