Noninvasive rheological inference from stable flows in confined tissues

TL;DR

This paper presents a noninvasive assay that uses collective cell migration to measure the rheological properties of epithelial tissues, enabling high-throughput and direct inference of tissue mechanics from image data.

Contribution

The study introduces a novel, self-driven rheometer-like method for quantifying tissue rheology through collective migration, validated by a wet vertex-model framework.

Findings

Tissue exhibits persistent rotation and shear in patterned rings.

A Maxwell-like viscoelastic relation is identified in cell deformation and neighbor exchange.

The method discriminates roles of myosin II isoforms in tissue mechanics.

Abstract

Quantifying the in-plane rheology of epithelial monolayers remains challenging due to the difficulty of imposing controlled shear. We introduce a self-driven, rheometer-like assay in which collective migration generates stationary shear flows, allowing rheological parameters to be inferred directly from image sequences. The assay relies on two sets of ring-shaped fibronectin patches, micropatterned in arrays for high-throughput imaging. Within isolated rings, the epithelial tissue exhibits persistent rotation, from which we infer active migration stresses and substrate friction. Within partially overlapping rings, the tissue exhibits sustained shear, from which we infer the elastic and viscous responses of the cells. The emergence of a Maxwell-like viscoelastic relation -- characterized by a linear relationship between mean cell deformation and neighbor-exchange rate -- is specifically recapitulated within a wet vertex-model framework, which reproduces experimental measurements only when intercellular viscous dissipation is included alongside substrate friction. We apply our method to discriminate the respective roles of two myosin~II isoforms in tissue mechanics. Overall, by harnessing self-generated stresses instead of externally imposed ones, we propose a noninvasive route to rheological inference in migrating epithelial tissues and, more generally, in actively flowing granular materials.