Epithelial tissues fulfil many essential functions within organisms due to their ability to undergo large deformations without damage. Alteration of tissue mechanical properties can lead to fracture, resulting in serious disorders. Despite the severe consequences, our knowledge of the biophysical processes that govern tissue fracture remains limited [1]. Fracture in cellularised materials is a multiscale process involving the unzipping of molecular bonds at cell connections in response to stresses arising at the tissue level. Predicting whether and how a tissue with given mechanical properties will break in response to a generic load necessitates accounting for both the unbinding of bonds and the complex rheological behaviour typical of soft tissues—comprising a viscoelastic response and nonlinear behaviour at large deformations.
New experimental data on standardised in-vitro epithelial monolayers shows that, when the loading rate is increased, the rupture stress of monolayers increases while the rupture strain decreases [2]. This behaviour disappears when intermediate filaments are disrupted, suggesting that they are key players in this unusual behaviour.
We have developed a tissue model that accounts for the progressive recruitment of IFs as strain increases and for the remodelling of the IFs network under tension. The physical model shows that the mechanical response of such monolayers results from a combination of non-linear stiffening and viscoelasticity of the IFs [2]. By combining this novel tissue rheological model with the dynamics of receptor-ligand bonds at junctions between cells, we successfully capture the onset of fracture for different strain rates. To obtain information about the fracture propagation within the tissue, micromechanical features are currently being incorporated within our novel rheological model to reproduce the tissue organization at cell level.
References
[1] Bonfanti, A., Duque, J., Kabla, A., & Charras, G. “Fracture in living tissues”. Trends in Cell Biology, 32(6), (2022).
[2] Duque, J., Bonfanti, A., Fouchard, J., ..., Kabla, A. & Charras, G, “Rupture Strength of Living Cell Monolayers”. bioRxiv, (2024, to appear in Nature Materials)