Understanding the mechanical control of cell extrusion in collective assemblies (DeadorAlive)

Epithelia are assemblies of multiple cells whose complex dynamic behavior relies on physical properties including jamming-unjamming mechanisms, active turbulence and active nematic principles.

The homeostasis of epithelia is crucial to maintain barrier function and integrity while epithelial cells are constantly challenged by the environment.

To face these challenges, epithelia are dynamics and have to deal constantly with cell renewal and apoptotic extrusion, whose balance is key for epithelia homeostasis.

On top of this role in tissue homeostasis, cell extrusion is a major cause of tissue shape changes and tumor progression.

Extrusion mechanisms can thus lead to different cell fates namely dead or live cells but the factors selecting different cell fates are unknown.

Extruding cells and their neighbors experience various mechanical stresses that lead to cell shape changes and could determine the way cells are extruded and their fate. However, these mechanical stresses and their impact on tissue organization remain to be determined.

From our recent study on emergent active nematic properties of epithelia, we hypothesize that mechanical constraints coming from the active forces generated by neighboring cells and the passive physical properties of the environment can determine the modes of cell extrusion and the fate of extruded cells.

Here we propose to tackle the molecular mechanisms and physical principles that determine the manner by which cells are extruded and the collective response of surrounding cells, and to evaluate their contribution in tissue homeostasis, morphogenesis and tumor progression.

By combining tools from soft matter physics, cell biology and engineering, our project will reveal how active and passive physical signals are overarching components of the behaviors of tissues at different temporal and spatial scales, and may further establish novel paths to understand the mechanobiology of epithelial tissues in normal and pathological conditions.