Disentangling the role of rheology in predicting tissue fracture

Speaker: Alessandra Bonfanti, University of Bergamo

Authors: Bonfanti A., Kaplan, J., Fouchard J., Duque J., Khalilgharibi, N., Charras G., Kabla A.

Abstract: Soft biological tissues fulfil many essential functions within organisms due to their ability to undergo large deformations without damage. Even in response to physiological deformations, alteration of tissue mechanical properties can lead to fracture, resulting in serious disorders. Despite the severe consequences of tissue failure, our knowledge of the biophysical processes that governs tissue fracture remains limited. Tissue fracture is a multiscale process involving the unzipping of intercellular adhesions at intercellular junctions connections in response to stresses arising at the tissue level that are transmitted to adhesion complexes via the cytoskeleton. Predicting whether and how a tissue with given mechanical properties will break in response to a well-defined load or loading history necessitates understanding not only the unbinding of bonds under force but also the complex rheological behaviour arising in soft tissues in response to large deformations. Experimental data on in-vitro MDCK epithelial monolayers (a simple yet physiologically relevant soft tissue) shows that the rupture stress of monolayers increases with loading rate but, intriguingly, the rupture strain decreases. The experiments also suggest that, in addition to actomyosin, intermediate filaments are key players in this unusual behaviour. Using a computational model, we show that the unusual mechanical response results from a combination of non-linear stiffening and visco-elasticity of the cytoskeleton. The model accounts for the progressive recruitment of intermediate filaments as strain is increased, the remodelling of such network under tension, and the dynamics of receptor-ligand bonds at junctions between cells. The model is effective at capturing the rheology of the tissue before fracture and its relationship to the onset of failure. It also illustrates the interplay between different molecular structures to regulate the response of living tissues, and how these could be integrated to form empirical descriptions of the overall material behaviour. Together with the experimental data, the simulations clarify how strain stiffening can effectively protect tissues against rupture and how pathologies affecting intercellular junctions and intermediate filaments lead to tissue fragilisation.

Biography: After graduating in Mechanical Engineering at the University of Bergamo, I moved to the University of Southampton where I obtained my PhD in Engineering. During this time I worked on the plastic response of cellular materials for biomedical applications. While completing my PhD, I was involved in the modelling of the mechanical properties of fibrotic tissues for the design of new treatments. At this time, I became fascinated by the significant impact that mechanobiology can have in the development of new diagnostic tools and treatments, and for the understanding of disease progression. For this reason, I decided to join Prof Kabla’s group at the University of Cambridge where I worked on the modelling of epithelial monolayers with particular focus on their rheological properties. I am currently a Research Fellow at Politecnico di Milano where I am continuing to study the mechanical response of tissues, in particular their fracture behaviour.