Mechanobiological mechanism of cyclic stretch-induced cell columnarization

• DOI: 10.1016/j.celrep.2025.115662
• Publication Date: 2025-05-07T00:12:23Z
• Authors: Lun-Wei Lee; Gang-Hui Lee; I-Hsiu Su; Chia-Hsuan Lu; Keng-Hui Lin; Fu-Lai Wen; Ming-Jer Tang

In vivo, epithelial cells maintain structural integrity under dynamic mechanical perturbations. To study this, we treated various cell lines with long-term cyclic stretch (CS). Surprisingly, transitioned from cuboidal to columnar shape (columnarization) in MDCK cells, while others only elongated. This change correlated actin accumulation at the top and stress fiber realignment bottom. Blocking stimulation via FAK inhibition or reducing vinculin partially prevented columnarization; however, disrupting tight junctions cellular contractility substantially blocked it. The MK4 derived weaker cell-cell junctions, showed less columnarization CS, whereas overexpressing Caveolin-1 (Cav1) enhanced promoted formation. Atomic force microscopy studies revealed increased apical junctional stiffness both CS-treated Cav1-overexpressing cells. This, combined a mathematical model, elucidated physical characteristics changes tension post-stretch, revealing mechanobiological foundation of columnarization.