Mechanical stress driven by rigidity sensing governs epithelial stability

Abstract

Epithelia act as a barrier against environmental stress and abrasion and in vivo they are continuously exposed to environments of various mechanical properties. The impact of this environment on epithelial integrity remains elusive. By culturing epithelial cells on 2D hydrogels, we observe a loss of epithelial monolayer integrity through spontaneous hole formation when grown on soft substrates. Substrate stiffness triggers an unanticipated mechanical switch of epithelial monolayers from tensile on soft to compressive on stiff substrates. Through active nematic modelling, we find unique patterns of cell shape texture called nematic topological defects that underpin large isotropic stress fluctuations at certain locations thereby triggering mechanical failure of the monolayer and hole opening. Our results show that substrate stiffness provides feedback on monolayer mechanical state and that topological defects can trigger stochastic mechanical failure, with potential application towards a mechanistic understanding of compromised epithelial integrity in bacterial infection, tumor progression and morphogenesis.

Bridging microscopic cell dynamics to nematohydrodynamics of cell monolayers

“…Appearance of cell-free space has been linked to viscoelastic properties of the substrate [56]. More recently, Sonam et al [57] have suggested that the spontaneous formation of holes within cell monolayer can occur due to the heterogeneity in substrate stiffness and using a vertex model they show that the gaps can form in the areas close to negative half-integer topological defects, which result in higher tensile stresses within the cell layer. Thus, extending the model to account for substrate heterogeneity will provide a theoretical platform to study the gap formation and its implications on collective cell movement.…”

Bridging microscopic cell dynamics to nematohydrodynamics of cell monolayers

“…58 Appearance of cell-free space has been linked to viscoelastic properties of the substrate. 59 More recently, Sonam et al 60 have suggested that the spontaneous formation of holes within cell monolayer can occur due to the heterogeneity in substrate stiffness and using a vertex model they show that the gaps can form in the areas close to negative half-integer topological defects, which result in higher tensile stresses within the cell layer. Thus, extending the model to account for substrate heterogeneity will provide a theoretical platform to study the gap formation and its implications on collective cell movement.…”

Modulation of Calcium Signaling and Metabolic Pathways in Endothelial Cells with Magnetic Fields

“…Vascular endothelial cells, which form the inner lining of the blood vessel wall and are directly exposed to blood flow and corresponding shear stress, serve crucial homeostatic functions in response to various chemical and mechanical stimuli [82,83].…”