Spatiotemporal dynamics of PIEZO1 localization controls keratinocyte migration during wound healing

• DOI: 10.7554/elife.65415
• Publication Date: 2021-09-27T12:24:17Z
• Authors: Jesse R Holt; Wei-Zheng Zeng; Elizabeth L Evans; Seung-Hyun Woo; Shang Ma; Hamid Abuwarda; Meaghan Loud; Ardem Patapoutian; Medha M Pathak
• Keywords: Piezo1; Epidermis (zoology); Live cell imaging

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