Abstract

The collective migration of keratinocytes during wound healing requires both the generation and transmission of mechanical forces for individual cellular locomotion and the coordination of movement across cells. Leader cells along the wound edge transmit mechanical and biochemical cues to ensuing follower cells, ensuring their coordinated direction of migration across multiple cells. Despite the observed importance of mechanical cues in leader cell formation and in controlling coordinated directionality of cell migration, the underlying biophysical mechanisms remain elusive. The mechanically-activated ion channel PIEZO1 was recently identified to play an inhibitory role during the reepithelialization of wounds. Here, through an integrative experimental and mathematical modeling approach, we elucidate PIEZO1's contributions to collective migration. Time-lapse microscopy reveals that PIEZO1 activity inhibits leader cell formation at the wound edge. To probe the relationship between PIEZO1 activity, leader cell formation and inhibition of reepithelialization, we developed an integrative 2D continuum model of wound closure that links observations at the single cell and collective cell migration scales. Through numerical simulations and subsequent experimental validation, we found that coordinated directionality plays a key role during wound closure and is inhibited by upregulated PIEZO1 activity. We propose that PIEZO1-mediated retraction suppresses leader cell formation which inhibits coordinated directionality between cells during collective migration.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

* Manuscript edited in places for clarity.

Details

Title
PIEZO1 regulates leader cell formation and cellular coordination during collective keratinocyte migration
Author
Chen, Jinghao; Holt, Jesse R; Evans, Elizabeth L; Lowengrub, John S; Pathak, Medha M
University/institution
Cold Spring Harbor Laboratory Press
Section
New Results
Publication year
2024
Publication date
Mar 6, 2024
Publisher
Cold Spring Harbor Laboratory Press
ISSN
2692-8205
Source type
Working Paper
Language of publication
English
ProQuest document ID
2731906455
Copyright
© 2024. This article is published under http://creativecommons.org/licenses/by/4.0/ (“the License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.