Collective cell migration and residual stress accumulation: modeling 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 (up to ~100 - 150 Pa). Compressive stress is primarily accumulated (1) within a core region of migrating cell clusters during their movement through the dense environment and (2) 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 compressive stress. Shear stress of a few Pa significantly influences cell state. Deeper insight into cell strategy to minimize undesirable shear stress is a priority in order to understand various biological processes such as morphogenesis, wound healing and cancer invasion. We pointed out to cause-consequence relations of these complex phenomena based on rheological modeling consideration in order to stimulate further experimental work. Cell strategy should be connected with the type and distribution of adhesion contacts such as adherens junctions and tight junctions per migrating clusters in order to (1) reinforce the cluster structure perpendicular to the direction of cell migration and (2) ensure structural elasticity of cluster in the direction of migration. These conditions lead to the stiffness inhomogeneity per single migrating clusters. Cell strategy should also be related to the state of the perturbed boundary layer around the cluster in the context of its thickness and slip effects. Statement of SignificanceCollective cell migration induces a local generation of stress (normal and shear) significant even in 2D (up to 100-150 Pa). Cells well tolerate compressive stress up to a few kPa. However, shear stress of a few Pa can induce severe damage to vimentin and keratin intermediate filament networks during 1 h, while shear stress of ~60 Pa can cause the inflammation in epithelial cells during 5.5 h. Deeper insight into cell strategy to minimize undesirable shear stress is a priority in order to understand various biological processes. Cell strategy should be connected with the type and distribution of adhesion contacts such as adherens junctions and tight junctions per migrating clusters and surrounding perturbed boundary layers.