Interfacial tension and growth both contribute to mechanical cell competition

Abstract

Tissue plasticity and homeostasis rely on the mutual interplay between cell behaviour and mechanical inputs1. Yet, mechanical stress can also contribute to the evolution of some pathologies, notably by accelerating pretumoural cell expansion through the process of mechanical cell competition2-5. Mechanical cell competition is a conserved process in which one cell population is preferentially eliminated when mixed with another cell population due to its higher sensitivity to mechanical stress2,3,5-8. Most of the recent theoretical and experimental explorations of mechanical cell competition focused so far on the contribution of growth and pressure to cell elimination and were limited to few genetic contexts, including the activation of Ras in vivo2,8, and the mutation of the polarity gene scribble in mammalian cell culture3,4,9. However, it remains unclear whether other oncogenes can trigger similar mechanisms and whether growth is generally the only central regulator of cell compaction and cell elimination. Using the Drosophila pupal notum (a single layer epithelium), quantitative live imaging and vertex modelling, we revisited the mechanisms contributing to cell compaction and cell elimination during mechanical cell competition. Doing so, we outlined the co-existence of two modes of wild type (WT) cell compaction near oncogenic cells, namely the compaction driven by growth versus local compaction driven by increased tension at tumoural/WT cell interfaces in zones of high curvature (similar to "Laplace pressure"). We highlighted distinctive signatures in cell deformation and cell elimination distribution that can delineate these two modes of compaction, and we recapitulated them in silico and in vivo using genetic backgrounds affecting growth and/or interfacial tension independently. Altogether, this study reveals for the first time the contribution of interfacial tension-driven compaction to mechanical cell competition and outlines the co-existence of various modes of compaction during cell elimination and pretumoural clone expansion.