Distribution and propagation of mechanical stress in simulated structurally heterogeneous tissue spheroids
Maxim Cuvelier, Jiří Pešek, Ioannis Papantoniou, Herman Ramón, Bart Smeets
Abstract
The mechanical microenvironment of cells has been associated with phenotypic changes that cells undergo in three-dimensional spheroid culture formats. Radial asymmetry in mechanical stress - with compression in the core and tension at the periphery - has been analyzed by representing tissue spheroids as homogeneous visco-elastic droplets under surface tension. However, the influence of the granular microstructure of tissue spheroids in the distribution of mechanical stress in tissue spheroids has not been accounted for in a generic manner. Here, we quantify the distribution and propagation of mechanical forces in structurally heterogeneous multicellular assemblies. For this, we perform numerical simulations of a deformable cell model, which represents cells as elastic, contractile shells surrounding a liquid incompressible cytoplasm, interacting by means of non-specific adhesion. Using this model, we show how cell-scale properties such as cortical stiffness, active tension and cell-cell adhesive tension influence the distribution of mechanical stress in simulated tissue spheroids. Next, we characterize the transition at the tissue-scale from a homogeneous liquid droplet to a heterogeneous packed granular assembly.