Myosin-II dependent cell contractility contributes to spontaneous nodule formation of mesothelioma cells

TL;DR

This study reveals that mesothelioma cell nodule formation is driven by Myosin II-dependent contractility rather than proliferation, and can be controlled by pharmacological inhibitors, with a mechanical model explaining the patterning process.

Contribution

It introduces a cell-resolved mechanical model and demonstrates the role of contractility in nodule formation, offering new insights into mesothelioma cell patterning mechanisms.

Findings

Nodules form via contractility, not proliferation.

Pharmacological inhibitors can prevent or reverse nodule formation.

Mechanical tension influences nodule size, shape, and formation speed.

Abstract

We demonstrate that characteristic nodules emerge in cultures of several malignant pleural mesothelioma (MPM) cell lines. Instead of excessive local cell proliferation, the nodules arise by Myosin II-driven cell contractility. The aggregation process can be prevented or reversed by suitable pharmacological inhibitors of acto-myosin contractility. A cell-resolved elasto-plastic model of the multicellular patterning process indicates that the morphology and size of the nodules as well as the speed of their formation is determined by the mechanical tension cells exert on their neighbors, and the stability of cell-substrate adhesion complexes. A linear stability analysis of a homogenous, self-tensioned Maxwell fluid indicates the unconditional presence of a patterning instability.