Spatial confinement induces oscillatory migration of epidermal keratinocytes and forms a three-compartment epithelial structure with epithelial–mesenchymal transition dynamics
4 affiliations
- 1Department of Dermatology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan
- 2Research Center of Mathematics for Social Creativity, Research Institute for Electronic Science, Hokkaido University, Sapporo, Japan
- 3Department of Physics, Graduate School of Science, Chiba University, Chiba, Japan
- 4Department of Molecular Biology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan
Abstract
Epithelial cells undergo epithelial–mesenchymal transition (EMT) during migration and regain their epithelial phenotype in the post-migration phase (mesenchymal–epithelial transition [MET]). We established an experimental system that reproduces a three-compartment epithelial structure comprising the original epithelium, its EMT state, and its MET state. Keratinocytes (KCs), skin epithelial cells, placed on a microporous membrane, migrated through 3.0 µm or larger micropores. The 3.0-µm-pored membrane induced an epithelial structure with three distinct states: stratified KCs above the membrane, KCs showing EMT within the micropores, and a new stratified epithelium under the membrane. The membrane with larger micropores failed to maintain the three-compartment epithelial structure. Live imaging revealed that KCs moved in an oscillatory manner, with actin-rich filopodia-like structures extending into and out of the 3.0 µm micropores, while the cells migrated unidirectionally into larger micropores. Piezo1 and keratin 6 were identified as negative modulators of KC entry into and exit from the 3.0 µm micropores. These results demonstrate that non-cancerous epithelial cells migrate through confined spaces in an oscillatory manner, which might contribute to the formation of a three-compartment epithelial structure that recapitulates key aspects of wound healing.
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BibTeX
@article{nohara2026spatial,
title = {{Spatial confinement induces oscillatory migration of epidermal keratinocytes and forms a three-compartment epithelial structure with epithelial–mesenchymal transition dynamics}},
author = {Takuma Nohara and Sota Itamoto and Junichi Kumamoto and Yosuke Mai and Mayuna Shimano and Sora Kato and Hiroyuki Kitahata and Hideki Nakamura and Shota Takashima and Mika Watanabe and Masaharu Nagayama and Tsukasa Oikawa and Hideyuki Ujiie and Ken Natsuga},
journal = {eLife},
year = {2026},
month = nov,
doi = {10.7554/elife.105192},
url = {https://elifesciences.org/articles/105192},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Spatial confinement induces oscillatory migration of epidermal keratinocytes and forms a three-compartment epithelial structure with epithelial–mesenchymal transition dynamics
AU - Takuma Nohara
AU - Sota Itamoto
AU - Junichi Kumamoto
AU - Yosuke Mai
AU - Mayuna Shimano
AU - Sora Kato
AU - Hiroyuki Kitahata
AU - Hideki Nakamura
AU - Shota Takashima
AU - Mika Watanabe
AU - Masaharu Nagayama
AU - Tsukasa Oikawa
AU - Hideyuki Ujiie
AU - Ken Natsuga
PY - 2026
DA - 2026/11/06
JO - eLife
DO - 10.7554/elife.105192
UR - https://elifesciences.org/articles/105192
AB - Epithelial cells undergo epithelial–mesenchymal transition (EMT) during migration and regain their epithelial phenotype in the post-migration phase (mesenchymal–epithelial transition [MET]). We established an experimental system that reproduces a three-compartment epithelial structure comprising the original epithelium, its EMT state, and its MET state. Keratinocytes (KCs), skin epithelial cells, placed on a microporous membrane, migrated through 3.0 µm or larger micropores. The 3.0-µm-pored membrane induced an epithelial structure with three distinct states: stratified KCs above the membrane, KCs showing EMT within the micropores, and a new stratified epithelium under the membrane. The membrane with larger micropores failed to maintain the three-compartment epithelial structure. Live imaging revealed that KCs moved in an oscillatory manner, with actin-rich filopodia-like structures extending into and out of the 3.0 µm micropores, while the cells migrated unidirectionally into larger micropores. Piezo1 and keratin 6 were identified as negative modulators of KC entry into and exit from the 3.0 µm micropores. These results demonstrate that non-cancerous epithelial cells migrate through confined spaces in an oscillatory manner, which might contribute to the formation of a three-compartment epithelial structure that recapitulates key aspects of wound healing.
SN - 2050-084X
ER -