Why are isolated and collective cells greatly different in stiffness?

Epithelial monolayers play a vital role in gastrulation, embryonic development and tumor metastasis, and protect the organs from pathogens. Experiments showed that the elastic stiffness of epithelial monolayers, though composed of cells, is two orders of magnitude higher than that of the isolated cells. Here we propose a cytoskeleton-based model to investigate the mechanics of an epithelial monolayer. Both the two- and three-dimensional models demonstrate that a cell monolayer can be far stiffer in the in-plane direction than a single cell, because the cytoskeletal structural rotation in the monolayer is geometrically constrained by neighboring cells. With the increase in the transverse size or the decrease in the thickness of the monolayer, the constraint effect on structural rotation becomes stronger. In addition, a phase diagram for the modulus ratio between a monolayer and an isolated cell is established with respect to the interfacial tension and the molecular contraction level. This theoretical model can not only deepen our understanding of the behavior of collective cells, and but also shed light on linking cell mechanics to mechanical properties and biological functions of tissues.