The role of viscoelasticity in long time cell rearrangement

Cell rearrangement caused by collective cell migration (CCM) during free expansion of epithelial monolayers has become a landmark in our current understanding of fundamental biological processes such as tissue development, regeneration, wound healing or cancer invasion. Cell spreading causes formation of mechanical waves which has a feedback effect on cell rearrangement and can lead to the cell jamming state. The mechanical waves describe oscillatory changes in cell velocity, as well as, the rheological parameters that affect them. The velocity oscillations, obtained at a time scale of hours, are in the form of forward and backward flows. Collision of forward and backward flows can induce an increase in the cell compressive stress accompanied with cell packing density which have a feedback impact on cell mobility, tissue viscoelasticity and alters the tissue stiffness. The tissue stiffness depends on the cell packing density and the active/passive (i.e. migrating/resting) state of single cells and can be used as an indicator of cell jamming state transition. Since cell stiffness can be measured it may directly show in which state the multicellular system is. In this work a review of existing modeling approaches is given along with assortment of published experimental findings, in order to invite experimentalists to test given theoretical considerations in multicellular systems.