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PreprintCC BY-NC-NDbioRxiv

Local mechanical heterogeneity drives epidermal cell delamination

1 more authors
  1. 1Universite Paris Cite, CNRS, Institut Jacques Monod, F-75013 Paris, France

Abstract

Delamination within stratified epithelia like the skin epidermis describes the detachment and upward motion of cells originating from the basal layer. Despite its fundamental importance for tissue development, homeostatic regeneration and repair, the mechanisms that drive delamination remain a longstanding open question. Upward motion follows cell shape changes, which are inherently driven by physical forces, but their role is elusive. Here, we investigate delamination in stratifying keratinocytes by combining imaging, force measurements and theoretical modeling. We identify a local change in force balance between differentiating cells and their environment as the key step initiating delamination. Within a homogeneous cell layer with apically polarized contractility, differentiation leads to actomyosin remodeling, redistributing cellular force exertion to the basal side. Such mechanical heterogeneity then results in differentiating cells experiencing and inward basal and outward apical forces that manifest in the formation of a +1 force defect and promote shape changes culminating in upward motion. Simultaneously, delaminating cells actively pull on their underlying neighbors, generating convergent tissue flows which close the basal layer below. Together, we propose a general physical description of delamination initiation, which may act across various multilayered epithelia.

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BibTeX
@misc{schoenit2026local,
  title = {{Local mechanical heterogeneity drives epidermal cell delamination}},
  author = {A. Schoenit and J. O'Byrne and C. Daubech and W. Schmidt and L. Anger and Y. Shen and M. Ruebsam and R. Dubrall and F. Wodrascka and R. Voituriez and B. Ladoux and C. M. Niessen and R.-M. Mege},
  howpublished = {bioRxiv},
  year = {2026},
  month = aug,
  doi = {10.64898/2026.08.30.747990},
  url = {https://www.biorxiv.org/content/10.64898/2026.08.30.747990v1},
  note = {CC BY-NC-ND},
}
RIS
TY  - UNPB
TI  - Local mechanical heterogeneity drives epidermal cell delamination
AU  - A. Schoenit
AU  - J. O'Byrne
AU  - C. Daubech
AU  - W. Schmidt
AU  - L. Anger
AU  - Y. Shen
AU  - M. Ruebsam
AU  - R. Dubrall
AU  - F. Wodrascka
AU  - R. Voituriez
AU  - B. Ladoux
AU  - C. M. Niessen
AU  - R.-M. Mege
PY  - 2026
DA  - 2026/08/30
PB  - bioRxiv
DO  - 10.64898/2026.08.30.747990
UR  - https://www.biorxiv.org/content/10.64898/2026.08.30.747990v1
AB  - Delamination within stratified epithelia like the skin epidermis describes the detachment and upward motion of cells originating from the basal layer. Despite its fundamental importance for tissue development, homeostatic regeneration and repair, the mechanisms that drive delamination remain a longstanding open question. Upward motion follows cell shape changes, which are inherently driven by physical forces, but their role is elusive. Here, we investigate delamination in stratifying keratinocytes by combining imaging, force measurements and theoretical modeling. We identify a local change in force balance between differentiating cells and their environment as the key step initiating delamination. Within a homogeneous cell layer with apically polarized contractility, differentiation leads to actomyosin remodeling, redistributing cellular force exertion to the basal side. Such mechanical heterogeneity then results in differentiating cells experiencing and inward basal and outward apical forces that manifest in the formation of a +1 force defect and promote shape changes culminating in upward motion. Simultaneously, delaminating cells actively pull on their underlying neighbors, generating convergent tissue flows which close the basal layer below. Together, we propose a general physical description of delamination initiation, which may act across various multilayered epithelia.
ER  -