Altering Cell Junctional Tension in Spheroids through E-Cadherin Engagement Modulation

Abstract

Cadherin-mediated tension at adherens junctions (AJs) is fundamental for cell−cell adhesion and maintaining epithelial integrity. Despite the importance of manipulating AJs to dissect cell−cell interactions, existing three-dimensional (3D) multicellular models have not adequately addressed the precise manipulation of these junctions. To fill this gap, we introduce Ecadherin-modified tension gauge tethers (TGTs) at the junctions within spheroids. The system enables both quantification and modulation of junctional tension with specific DNA triggers. Using rupture-induced fluorescence, we successfully measure mechanical forces in 3D spheroids. Furthermore, mechanically strong TGTs can maintain normal E-cadherin-mediated adhesion. Employing toehold-mediated strand displacement allowed us to disrupt Ecadherin-specific cell−cell adhesion, consequently altering intracellular tension within the spheroids. Our methodology offers a robust and precise way to manipulate cell−cell adhesion and intracellular mechanics in spheroid models.