Experimental determination of the stress-free spontaneous cell shape in epithelial monolayers

Determine the experimentally observable nature of the stress-free spontaneous two-dimensional geometrical shape of epithelial cells in confluent monolayers, quantified by the cell shape index defined as perimeter divided by the square root of area, which serves as a central input to vertex-model descriptions of the liquid-to-solid jamming transition.

Background

The vertex model of epithelial mechanics and jamming uses the stress-free spontaneous cell shape (shape index) as a key input parameter. Despite its importance for predicting transitions between liquid-like and solid-like tissue states, the experimentally accessible nature of this spontaneous geometrical shape has not been established.

In this work, the authors use a restrained trypsinization (deadhesion) assay to probe cell rounding dynamics, offering a route to infer aspects of stress-free morphology. However, they explicitly state that the spontaneous geometrical shape remains completely unknown experimentally, motivating a precise experimental characterization.

References

The concept of spontaneous shape plays a major role in interpreting collective behaviors in dense epithelial tissues, specifically, the liquid-like to solid-like jamming transition that is predicted by the framework of the vertex model10,18,32. The vertex model takes, as a central input parameter, the stress-free spontaneous 2D shape index (SI = p/VA , p - perimeter, A - area) of cells. However, the nature of that spontaneous geometrical shape is completely unknown experimentally.

— Cycling and tensed cells interpenetrated by non-cycling and compressed cells form a critical epithelial reticulum (2509.16661 - Daraf et al., 20 Sep 2025) in Extended data Fig. 2 caption