Targeted elimination of mesenchymal-like cancer cells through cyclic stretch activation of Piezo1 channels: the physical aspects.

Abstract

The application of cyclic stretch could represent a novel therapeutic method for fighting cancer. Research indicates that this mechanical stimulus selectively induces cell death in cancer mesenchymal-like cells while enhancing the migration and proliferation of healthy epithelial cells. Although the mechanisms have been examined through the lenses of cell signalling, gene expression, and biochemical processes, a significant gap persists in our understanding of the physical factors that drive cellular responses. This study aims to clarify the importance of physical factors, particularly the viscoelastic characteristics of the cell membrane, including actin cytoskeleton and lipid bilayer, and how their coupling affects bilayer bending and activation of the mechanosensitive Piezo1 channels in response to cyclic stretch in both epithelial and cancer cells. The bending of the bilayer surrounding Piezo1 molecules affects their conformations, which in turn influences calcium influx. This bending is contingent upon the coupling between the cell membrane and extracellular matrix. The primary factors contributing to the mechanically induced apoptosis of cancer cells are the perturbation of intracellular calcium homeostasis and disruption of focal adhesions.