Abstract

Intercellular junctions are important mechanical couplers between cells in epithelial layers providing adhesion and intercellular communication. Regulation of the junctions occurs in cellular processes such as layer formation, epithelial-to-mesenchymal transition, embryogenesis, and cancer progression. Many studies addressed the role of force generation in cells for establishing lateral cell-cell junctions and the role of cellular force transmission in tissue formation and maintenance. Our atomic force microscopy- (AFM) based study shed light on the role of both, tight junctions and adherens junctions for the mechanical properties of individual epithelial cells that are part of a confluent monolayer. We found that tight junctions are important for the establishment of a functional barrier-forming layer but impairing them does not reduce the mechanical integrity of cells. Depletion of ZO-1 results in a weak increase in cortical tension. An opposite effect was observed for disruption of E-cadherin-mediated adherens junctions using DTT. Opening of adherens junctions leads to substantial alterations of cellular mechanics such as reduced overall stiffness, but these changes turned out to be reversible after re-establishing disulfide bridges in E-cadherin by removal of DTT. We found that regulatory mechanisms exist that preserve mechanical integrity during recovery of disrupted adherens junctions.

Highlights

  • Epithelial cells form a dense, stable cell layer lining the outer surface of tissue and organs

  • On the inner cellular site, it binds to zonula occludens, which establishes the contact to the F-actin cytoskeleton[8]

  • We used short interference RNA against zonula occudens-1 (ZO-1) in order to examine the role of tight junctions for the mechanical integrity of epithelial cells

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Summary

Introduction

Epithelial cells form a dense, stable cell layer lining the outer surface of tissue and organs. Mechanical strength and communication between the cells within a layer is provided by different cell adhesion sites including tight junctions (TJs)[1], adherens junctions (AJs)[2], desmosomes[3], and gap junctions[4]. Establishment of these intercellular junctions divides polarised cells in apical and basolateral divisions. Owing to their motility and dynamic conditions epithelia are capable of monitoring development[5], tissue healing[6], and cancer invasion[7]. Depending on the cell type different mechanisms might exist to regulate tension

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