THE ROLE OF MECHANICS AND COLLECTIVE CELL CONSTRAINTS IN EPITHELIAL CELL DEATH AND EXTRUSION

Abstract

Apoptotic extrusion expels caspase-activated (dead) cells from epithelia to preserve monolayer integrity. We aimed to study two aspects of the extrusion process: 1) After initiation, what mechanism(s) drive(s) extrusion completion? and 2) What triggers apoptotic extrusion in a naturally evolving epithelium? Extrusion of cells is usually thought to be completed by the intercellular, actin purse-string contraction in neighbor cells. First, we discovered that epithelia cell density acts as a driving parameter to determine more than one extrusion mechanism. Neighbor cell lamellipodia protrusion drives extrusion at low density while the purse-string contraction mechanism operates at high density. We further found the epithelium to act as an active, nematic, liquid crystal material, and the spontaneously occurring topological defects in the alignment of cells generate locally high compressive stress that triggers cell apoptosis before extrusion.