Spatial organization of the extracellular matrix regulates cell–cell junction positioning

TLDR

Epithelial organization relies on interactions with the extracellular matrix (ECM) and neighboring cells, yet the ECM’s role in shaping multicellular morphogenesis remains poorly understood. This study develops a minimal model to examine how ECM influences the spatial arrangement of intercellular junctions. Fibronectin micropatterns were employed to restrict cell–ECM adhesion sites, enabling controlled assessment of junction positioning. The results show that ECM proximity destabilizes junctions by imposing large perpendicular tensions, while junctions remain stable in ECM‑deprived regions with lower forces, indicating that ECM anisotropy directs cells to reposition junctions to minimize mechanical stress and revealing a morphogenetic role for ECM in junction regulation.

Abstract

The organization of cells into epithelium depends on cell interaction with both the extracellular matrix (ECM) and adjacent cells. The role of cell–cell adhesion in the regulation of epithelial topology is well-described. ECM is better known to promote cell migration and provide a structural scaffold for cell anchoring, but its contribution to multicellular morphogenesis is less well-understood. We developed a minimal model system to investigate how ECM affects the spatial organization of intercellular junctions. Fibronectin micropatterns were used to constrain the location of cell–ECM adhesion. We found that ECM affects the degree of stability of intercellular junction positioning and the magnitude of intra- and intercellular forces. Intercellular junctions were permanently displaced, and experienced large perpendicular tensional forces as long as they were positioned close to ECM. They remained stable solely in regions deprived of ECM, where they were submitted to lower tensional forces. The heterogeneity of the spatial organization of ECM induced anisotropic distribution of mechanical constraints in cells, which seemed to adapt their position to minimize both intra- and intercellular forces. These results uncover a morphogenetic role for ECM in the mechanical regulation of cells and intercellular junction positioning.