Disorder in cellular packing can alter proliferation dynamics to regulate growth

TL;DR

This paper demonstrates how cellular packing disorder influences proliferation and growth regulation in tissues, linking tissue geometry to cell cycle dynamics through coupled oscillator models.

Contribution

It introduces a model connecting cell contact signals and tissue disorder to growth regulation, highlighting a collective dynamical transition in cell proliferation.

Findings

Disorder in cell packing affects proliferation dynamics.

Homogenization of cell morphology correlates with growth arrest.

Contact signals trigger oscillation cessation leading to growth regulation.

Abstract

Controlling growth via cell division is crucial in the development of higher organisms, and yet the mechanisms through which this is achieved, e.g., in epithelial tissue, is not yet fully understood. We show that by coupling the cell cycle oscillator governing cell division to signals that encode inter-cellular contacts, this phenomenon can be seen as a collective dynamical transition in a system of coupled oscillators in lattices with changing degree of disorder. As the distribution of cellular morphological characteristics become more homogeneous over the course of development, the contact-induced signals to the cells increase beyond a critical value to trigger coordinated cessation of oscillations, eventually leading to growth arrest. Our results suggest that the global phenomenon of growth rate reduction as a tissue approaches its appropriate size is causally related to the increasingly regular geometry of local cell-cell contact interfaces.