Cadherin-Based Intercellular Adhesions Organize Epithelial Cell-Matrix Traction Forces

TL;DR

This study demonstrates how cadherin-based cell--cell adhesions influence the spatial distribution of traction forces in epithelial cell colonies, highlighting their role in mechanical coordination and tissue regulation.

Contribution

It combines experimental and theoretical approaches to show that cadherin adhesions modulate force transmission and spatial force organization in epithelial tissues.

Findings

Cadherin adhesions localize traction forces to colony periphery.

Loss of cadherin disrupts force coordination among cells.

A physical model reproduces force distribution changes with adhesion strength.

Abstract

Cell--cell and cell-matrix adhesions play essential roles in the function of tissues. There is growing evidence for the importance of crosstalk between these two adhesion types, yet little is known about the impact of these interactions on the mechanical coupling of cells to the extracellular-matrix (ECM). Here, we combine experiment and theory to reveal how intercellular adhesions modulate forces transmitted to the ECM. In the absence of cadherin-based adhesions, primary mouse keratinocytes within a colony appear to act independently, with significant traction forces extending throughout the colony. In contrast, with strong cadherin-based adhesions, keratinocytes in a cohesive colony localize traction forces to the colony periphery. Through genetic or antibody-mediated loss of cadherin expression or function, we show that cadherin-based adhesions are essential for this mechanical cooperativity. A minimal physical model in which cell--cell adhesions modulate the physical cohesion between contractile cells is sufficient to recreate the spatial rearrangement of traction forces observed experimentally with varying strength of cadherin-based adhesions. This work defines the importance of cadherin-based cell--cell adhesions in coordinating mechanical activity of epithelial cells and has implications for the mechanical regulation of epithelial tissues during development, homeostasis, and disease.