Collective cell migration and residual stress accumulation: Rheological consideration

Stress generation during collective cell migration represents one of the key factors which influence the configuration of migrating cells, viscoelasticity of multicellular systems and their inter-relation. Local generation of stress (normal and shear) is significant even in 2D. Normal stress is primarily accumulated within a core region of migrating cell clusters during their movement through the dense environment and during the collisions of migrating cell clusters caused by uncorrelated motility. Shear stress can be significant within perturbed boundary layers around migrating clusters. Cells are more sensitive to the action of shear stress compared with normal stress. Shear stress of a few Pa significantly influences cell state. Prior studies have shown that collectively migrating cells move in such a way to minimize this stress, but it has not yet been determined how cells effectively minimize it. Deeper insight into possible cell mechanisms for minimizing undesirable shear stress would be of great importance because it may help to direct morphogenesis, accelerate wound healing or prevent cancer invasion. In the proposed model three primary mechanisms in which cells may reduce shear are given: decreasing speed, tissue thickening, and/or reducing slip effects. Suggestions obtained from the proposed model indicate a need for further experimental studies that will reveal whether the heterogeneity in the cell-cell adhesion types correlates well with the stiffness inhomogeneity, or changes in the adhesion clustering, cytoskeletal linkage or some other modification to the adhesion complex (adherens junctions or tight junctions) are occurring to influence overall adhesive strength.