Spatiotemporal dynamics of piezo1 localization controls keratinocyte migration during wound healing

Jesse R. Holt, Wei Zheng Zeng, Elizabeth L. Evans, Seung Hyun Woo, Shang Ma, Hamid Abuwarda, Meaghan Loud, Ardem Patapoutian, Medha M. Pathak

Research output: Contribution to journalArticlepeer-review

45 Scopus citations


Keratinocytes, the predominant cell type of the epidermis, migrate to reinstate the epithelial barrier during wound healing. Mechanical cues are known to regulate keratinocyte re-epithelialization and wound healing however, the underlying molecular transducers and biophysical mechanisms remain elusive. Here, we show through molecular, cellular and organismal studies that the mechanically-activated ion channel PIEZO1 regulates keratinocyte migration and wound healing. Epidermal-specific Piezo1 knockout mice exhibited faster wound closure while gain-of-function mice displayed slower wound closure compared to littermate controls. By imaging the spatiotemporal localization dynamics of endogenous PIEZO1 channels we find that channel enrichment at some regions of the wound edge induces a localized cellular retraction that slows keratinocyte collective migration. In migrating single keratinocytes, PIEZO1 is enriched at the rear of the cell, where maximal retraction occurs, and we find that chemical activation of PIEZO1 enhances retraction during single as well as collective migration. Our findings uncover novel molecular mechanisms underlying single and collective keratinocyte migration that may suggest a potential pharmacological target for wound treatment. More broadly, we show that nanoscale spatiotemporal dynamics of Piezo1 channels can control tissue-scale events, a finding with implications beyond wound healing to processes as diverse as development, homeostasis, disease and repair.

Original languageEnglish (US)
Article numbere65415
StatePublished - Sep 2021
Externally publishedYes


  • Cell migration
  • Cell retraction
  • Collective cell migration
  • Ion channel dynamics
  • Keratinocyte re-epithelialization
  • Mechanically-activated ion channels
  • Mechanotransduction
  • Wound healing

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)


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