Assessing mechanical agency during apical apoptotic cell extrusion

iScience. 2024 Sep 23;27(11):111017. doi: 10.1016/j.isci.2024.111017. eCollection 2024 Nov 15.

Abstract

Homeostasis is necessary for epithelia to maintain barrier function and prevent the accumulation of defective cells. Unfit, excess, and dying cells in the larval zebrafish tail fin epidermis are removed via controlled cell death and extrusion. Extrusion coincides with oscillations of cell area, both in the extruding cell and its neighbors. Here, we develop a biophysical model of this process to explore the role of autonomous and non-autonomous mechanics. We vary biophysical properties and oscillatory behaviors of extruding cells and their neighbors along with tissue-wide cell density and viscosity. We find that cell autonomous processes are major contributors to the dynamics of extrusion, with the mechanical microenvironment providing a less pronounced contribution. We also find that some cells initially resist extrusion, influencing the duration of the expulsion process. Our model provides insights into the cellular dynamics and mechanics that promote elimination of unwanted cells from epithelia during homeostatic tissue maintenance.

Keywords: Bioinformatics; Biophysics; Cell biology.