Active Growth Layer Induced by Micromechanical Feedback Shapes Proliferating Cell Collectives

TL;DR

This paper demonstrates that micromechanical feedback alone can generate an active growth layer in proliferating cell collectives, influencing their expansion, morphology, and internal stress without biochemical regulation.

Contribution

It introduces a particle-based model showing how mechanical feedback creates a growth layer and explains colony dynamics, linking microscopic mechanics to macroscopic behavior.

Findings

Mechanical feedback alone can produce an active growth layer.

The model predicts fingering instabilities during expansion.

Mechanical feedback accelerates colony growth exponentially.

Abstract

Proliferating cell collectives often develop an active growth layer near their boundary that regulates expansion and morphology, as observed in systems ranging from bacterial biofilms to epithelial tissues and tumor spheroids. While such layers have been attributed to diverse mechanisms, their microscopic origin remains unclear in many situations. Here, we show that micromechanical feedback alone provides a minimal mechanism for their emergence. We introduce a particle-based model of non-motile proliferating cells in which growth is locally inhibited by compressive stress, coupling division to mechanical interactions and generating an active growth layer without biochemical regulation. An emergent mechanical length scale, denoted by $\chi$, sets the extent of the proliferative region and controls the system's behavior across scales, governing growth dynamics, morphology and organizing internal stress and velocity fields. Coarse-graining the model yields a continuum description with no adjustable parameters, providing a microscopic foundation for existing approaches. When the colony expands into a passive environment, we observe and characterize fingering instabilities driven purely by mechanical feedback. These instabilities can be tuned through the system geometry relative to $\chi$, and leads to an exponential acceleration of colony growth, enhancing the collective growth rate. We further establish a correspondence with nutrient-depletion models, providing a route to study the statistical properties of expanding fronts within a minimal microscopic framework.