Mechanobiological mechanism of cyclic stretch-induced cell columnarization
Summary: In vivo, epithelial cells maintain structural integrity under dynamic mechanical perturbations. To study this, we treated various epithelial cell lines with long-term cyclic stretch (CS). Surprisingly, cells transitioned from cuboidal to columnar shape (columnarization) in MDCK cells, while...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-05-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124725004334 |
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| author | Lun-Wei Lee Gang-Hui Lee I-Hsiu Su Chia-Hsuan Lu Keng-Hui Lin Fu-Lai Wen Ming-Jer Tang |
| author_facet | Lun-Wei Lee Gang-Hui Lee I-Hsiu Su Chia-Hsuan Lu Keng-Hui Lin Fu-Lai Wen Ming-Jer Tang |
| author_sort | Lun-Wei Lee |
| collection | DOAJ |
| description | Summary: In vivo, epithelial cells maintain structural integrity under dynamic mechanical perturbations. To study this, we treated various epithelial cell lines with long-term cyclic stretch (CS). Surprisingly, cells transitioned from cuboidal to columnar shape (columnarization) in MDCK cells, while others only elongated. This change correlated with actin accumulation at the top and stress fiber realignment at the bottom. Blocking mechanical stimulation via FAK inhibition or reducing vinculin partially prevented columnarization; however, disrupting tight junctions or cellular contractility substantially blocked it. The MK4 cells, derived from MDCK cells with weaker cell-cell junctions, showed less columnarization under CS, whereas overexpressing Caveolin-1 (Cav1) in MK4 cells enhanced junctions and promoted columnar formation. Atomic force microscopy studies revealed increased apical junctional stiffness in both CS-treated MDCK and Cav1-overexpressing MK4 cells. This, combined with a mathematical model, elucidated the physical characteristics and changes in cell tension post-stretch, revealing the mechanobiological foundation of epithelial cell columnarization. |
| format | Article |
| id | doaj-art-a22a005b348e4a33af85b2f0f9cb6c65 |
| institution | DOAJ |
| issn | 2211-1247 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj-art-a22a005b348e4a33af85b2f0f9cb6c652025-08-20T02:57:53ZengElsevierCell Reports2211-12472025-05-0144511566210.1016/j.celrep.2025.115662Mechanobiological mechanism of cyclic stretch-induced cell columnarizationLun-Wei Lee0Gang-Hui Lee1I-Hsiu Su2Chia-Hsuan Lu3Keng-Hui Lin4Fu-Lai Wen5Ming-Jer Tang6Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan; Department of Physiology, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan; International Center for Wound Repair and Regeneration, National Cheng Kung University, Tainan 70101, TaiwanInternational Center for Wound Repair and Regeneration, National Cheng Kung University, Tainan 70101, TaiwanInternational Center for Wound Repair and Regeneration, National Cheng Kung University, Tainan 70101, TaiwanDepartment of Computer Science, University of Oxford, Wolfson Building, Parks Road, Oxford OXI 3QD, UKInstitute of Physics, Academia Sinica, Taipei 11529, TaiwanDepartment of Physics and Center for Complex Systems, National Central University, Taoyuan 32001, Taiwan; Physics Division, National Center for Theoretical Sciences, Taipei 10617, Taiwan; Corresponding authorInstitute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan; Department of Physiology, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan; International Center for Wound Repair and Regeneration, National Cheng Kung University, Tainan 70101, Taiwan; Corresponding authorSummary: In vivo, epithelial cells maintain structural integrity under dynamic mechanical perturbations. To study this, we treated various epithelial cell lines with long-term cyclic stretch (CS). Surprisingly, cells transitioned from cuboidal to columnar shape (columnarization) in MDCK cells, while others only elongated. This change correlated with actin accumulation at the top and stress fiber realignment at the bottom. Blocking mechanical stimulation via FAK inhibition or reducing vinculin partially prevented columnarization; however, disrupting tight junctions or cellular contractility substantially blocked it. The MK4 cells, derived from MDCK cells with weaker cell-cell junctions, showed less columnarization under CS, whereas overexpressing Caveolin-1 (Cav1) in MK4 cells enhanced junctions and promoted columnar formation. Atomic force microscopy studies revealed increased apical junctional stiffness in both CS-treated MDCK and Cav1-overexpressing MK4 cells. This, combined with a mathematical model, elucidated the physical characteristics and changes in cell tension post-stretch, revealing the mechanobiological foundation of epithelial cell columnarization.http://www.sciencedirect.com/science/article/pii/S2211124725004334CP: Cell biology |
| spellingShingle | Lun-Wei Lee Gang-Hui Lee I-Hsiu Su Chia-Hsuan Lu Keng-Hui Lin Fu-Lai Wen Ming-Jer Tang Mechanobiological mechanism of cyclic stretch-induced cell columnarization Cell Reports CP: Cell biology |
| title | Mechanobiological mechanism of cyclic stretch-induced cell columnarization |
| title_full | Mechanobiological mechanism of cyclic stretch-induced cell columnarization |
| title_fullStr | Mechanobiological mechanism of cyclic stretch-induced cell columnarization |
| title_full_unstemmed | Mechanobiological mechanism of cyclic stretch-induced cell columnarization |
| title_short | Mechanobiological mechanism of cyclic stretch-induced cell columnarization |
| title_sort | mechanobiological mechanism of cyclic stretch induced cell columnarization |
| topic | CP: Cell biology |
| url | http://www.sciencedirect.com/science/article/pii/S2211124725004334 |
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