Yield stress: A tipping point of cell unjamming.

Abstract

Tissue mechanics is impacted not only by the properties of the composite cells, but also by the behavior of collective cells, such as cell unjamming and extended differential adhesion. In former studies, we used multicellular spheroids (MS) of healthy epithelial cells (jammed solid) and cancerous mesenchymal cells (unjammed fluid) as our model system to investigate the tissue mechanics of cell clusters. We realized even in a simple cell cluster system, the mechanical behavior differed between core/shell region, which we concluded due to the different domination of nuclei (bulk) and cortical rim formed by cell cytoskeleton (tissue surface tension). As we also observed in cancer spheroids, nuclei seem to dominate the whole mechanics of MTS (no reaction to chemical perturbation of the cell cytoskeleton). By specifically probing the nucleus region of a single cell under AFM, and combining its nucleus morphology aside as an indicator, we could measure how much yield stress a cell will need to become motile (unjammed). Based on our preliminary results, we see a different linear growth of the Young's modulus with elongated nuclei of healthy epithelial cells (high-slope) and cancerous mesenchymal cells (low-slope). Knowing the different behavior of such cell types under the constriction studies (mesenchymal cells do not pass through the confinement whereas epithelial cells do), the nuclei domination of the mesenchymal cells is unassailable. Therefore, to establish the connection between the nucleus-based yield stress to its motility are strongly required. To do so, we are able to derive an unjamming-based marker that detects the ability of cells to move in static histological images, which will be a big step to understand the role of the cancer cell unjamming in the metastatic cascade.