Proliferation-driven mechanical feedback regulates cell dynamics in growing tissues

TL;DR

This study uses agent-based simulations to explore how stress-dependent cell division and mechanical feedback influence cell dynamics in growing tissues, revealing diverse behaviors from jamming to hyperdiffusion.

Contribution

It uncovers the relationship between tissue growth laws, mechanical feedback, and cell motility, highlighting how feedback strength affects cell dynamics in tissue growth.

Findings

Cell dynamics range from jamming to hyperdiffusion depending on feedback.

Growth law exponent correlates with cell motility and feedback strength.

Higher proliferation rates lead to increased cell migration.

Abstract

Local stresses in a tissue, a collective property, regulate cell division and apoptosis. In turn, cell growth and division induce active stresses in the tissue. As a consequence, there is a feedback between cell growth and local stresses. However, how the cell dynamics depend on local stress-dependent cell division and the feedback strength is not fully understood. Here, we probe the consequences of stress-mediated growth and cell division on cell dynamics using agent-based simulations of a two-dimensional growing tissue. We discover a rich dynamical behavior of individual cells, ranging from jamming (mean square displacement, $\Delta (t) \sim t^{\alpha}$ with $\alpha$ less than unity), to hyperdiffusion ($\alpha > 2$) depending on cell division rate and the strength of the mechanical feedback. Strikingly, $\Delta (t)$ is determined by the tissue growth law, which quantifies cell proliferation (number of cells $N(t)$ as a function of time). The growth law ($N(t) \sim t^{\lambda}$ at long times) is regulated by the critical pressure that controls the strength of the mechanical feedback and the ratio between cell division-apoptosis rates. We show that $\lambda \sim \alpha$, which implies that higher growth rate leads to a greater degree of cell migration. The variations in cell motility are linked to the emergence of highly persistent forces extending over several cell cycle times. Our predictions are testable using cell-tracking imaging techniques.