A Mechanical Instability in Planar Epithelial Monolayers Leads to Cell Extrusion

Area of Science:

• Cell Biology
• Biophysics
• Tissue Engineering

Background:

• Cell extrusion, where a cell is expelled from an epithelial layer, is vital in development, homeostasis, and disease.
• While molecular mechanisms are known, the mechanical underpinnings of cell extrusion remain largely unexplored.

Purpose of the Study:

• To investigate the mechanical basis of cell extrusion using a computational model.
• To understand how geometric and force-based factors contribute to cell expulsion from epithelial monolayers.

Main Methods:

• Utilized a three-dimensional (3D) vertex model to simulate epithelial monolayers with 3D foam geometry.
• Analyzed the mechanical stability of the cellular arrangement under varying cell density and topological neighbor counts.
• Incorporated active contractile and adhesive forces to model genetically controlled cell behaviors.

Main Results:

• Homogeneous cell properties lead to extrusion when geometric symmetry is broken (e.g., increased density).
• Inherent mechanical instability in 3D epithelial foam geometry is sufficient to drive cell extrusion.
• Active cellular forces can direct extrusion apically or basally, depending on force balance.

Conclusions:

• Epithelial cell extrusion is fundamentally driven by mechanical instability and forces, not solely molecular cues.
• The findings align with in vivo observations and explain extrusions across various physiological and pathophysiological conditions.
• Provides a mechanical framework linking molecular regulation to physical processes in cell extrusion.