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Pajic-Lijakovic, I.

Publications and source records attributed to Pajic-Lijakovic, I..

3 recordsLinked to original sources

The role of viscoelasticity in long-time cell rearrangement

Although collective cell migration (CCM) is a highly coordinated and ordered migratory mode, perturbations in the form of mechanical waves appear even in 2D. These perturbations caused by the viscoelastic nature of cell rearrangement are involved in various biological processes, such as embryogenesis, wound healing and cancer invasion. The mechanical waves, as a product of the active turbulence occurred at low Reynolds number, represent an oscillatory change in cell velocity and the relevant rheological parameters. The velocity oscillations, in the form of forward and backward flows, are driven by: viscoelastic force, surface tension force, and traction force. The viscoelastic force represents a consequence of inhomogeneous distribution of cell residual stress accumulated during CCM. This cause-consequence relation is considered on a model system such as the cell monolayer free expansion. The collision of forward and backward flows causes an increase in cell packing density which has a feedback impact on the tissue viscoelasticity and on that base influences the tissue stiffness. The evidence of how the tissue stiffness is changed near the cell jamming is conflicting. To fill this gap, we discussed the density driven change in the tissue viscoelasticity by accounting for the cell pseudo-phase transition from active (contractile) to passive (non-contractile) state appeared near cell jamming in the rheological modeling consideration.

developmental biology↗

Viscoelasticity and cell jamming state transition

Although collective cell migration (CCM) is a highly coordinated migratory mode, perturbations in the form of jamming state transitions and vice versa often occur even in 2D. These perturbations are involved in various biological processes, such as embryogenesis, wound healing and cancer invasion. CCM induces accumulation of cell residual stress which has a feedback impact to cell packing density. Density-mediated change of cell mobility influences the state of viscoelasticity of multicellular systems and on that base the jamming state transition. Although a good comprehension of how cells collectively migrate by following molecular rules has been generated, the impact of cellular rearrangements on cell viscoelasticity remains less understood. Thus, considering the density driven evolution of viscoelasticity caused by reduction of cell mobility could result in a powerful tool in order to address the contribution of cell jamming state transition in CCM and help to understand this important but still controversial topic. In addition, five viscoelastic states gained within three regimes: (1) convective regime, (2) conductive regime, and (3) damped-conductive regime was discussed based on the modeling consideration with special emphasis of jamming and unjamming states.

developmental biology↗

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.

developmental biology↗