Epithelial Tissues from the Bottom-Up: Contact Inhibition, Wound Healing, and Force Networks

TL;DR

This paper presents a computational model of epithelial tissues that integrates cell mechanics and contact inhibition to explain tissue behavior during processes like wound healing and invasion.

Contribution

It introduces a novel model incorporating cell deformability, adhesion, and contact inhibition, linking cellular responses to tissue-level mechanical properties.

Findings

CIL reduces tissue density fluctuations.

CIL inhibits cell motion in steady states.

CIL accelerates wound healing by promoting cell movement in gaps.

Abstract

In processes such as embryo shaping, wound healing, and malignant cell invasion, epithelial cells transition between dispersed phases, where the cells move independently, and condensed phases, where they aggregate and deform to close gaps, forming confluent tissues. Understanding how cells regulate these transitions and how these transitions differ from those of inert particles remains an open challenge. Addressing these questions requires linking the macroscopic properties of tissues to the mechanical characteristics and active responses of individual cells, driven by sub-cellular processes. Here, we introduce a computational model that incorporates key factors such as cell deformability, lamellipodium-driven dynamics, cell-junction-mediated adhesion, and contact inhibition of locomotion (CIL)-a process where cells alter their motion upon contact with others. We demonstrate how these factors, along with cell density, regulate the dynamical and mechanical properties of tissues. We show that CIL imparts unique living-like behaviors to cells and tissues by reducing density fluctuations. This reduction in fluctuations affects the dynamics: it inhibits cell motion in steady states but promotes it in the presence of gaps, accelerating wound healing. Furthermore, the stabilization of tensile states by CIL, which would otherwise fracture, enables the formation of tensile force chains.