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Mechanically activated ion channel Piezo1 modulates macrophage polarization and stiffness sensing

Author

Listed:
  • Hamza Atcha

    (University of California Irvine
    University of California Irvine)

  • Amit Jairaman

    (University of California Irvine)

  • Jesse R. Holt

    (University of California Irvine
    University of California Irvine)

  • Vijaykumar S. Meli

    (University of California Irvine
    University of California Irvine
    University of California Irvine)

  • Raji R. Nagalla

    (University of California Irvine
    University of California Irvine)

  • Praveen Krishna Veerasubramanian

    (University of California Irvine
    University of California Irvine)

  • Kyle T. Brumm

    (University of California Irvine
    University of California Irvine)

  • Huy E. Lim

    (University of California Irvine
    University of California Irvine)

  • Shivashankar Othy

    (University of California Irvine)

  • Michael D. Cahalan

    (University of California Irvine)

  • Medha M. Pathak

    (University of California Irvine
    University of California Irvine
    University of California Irvine)

  • Wendy F. Liu

    (University of California Irvine
    University of California Irvine
    University of California Irvine)

Abstract

Macrophages perform diverse functions within tissues during immune responses to pathogens and injury, but molecular mechanisms by which physical properties of the tissue regulate macrophage behavior are less well understood. Here, we examine the role of the mechanically activated cation channel Piezo1 in macrophage polarization and sensing of microenvironmental stiffness. We show that macrophages lacking Piezo1 exhibit reduced inflammation and enhanced wound healing responses. Additionally, macrophages expressing the transgenic Ca2+ reporter, Salsa6f, reveal that Ca2+ influx is dependent on Piezo1, modulated by soluble signals, and enhanced on stiff substrates. Furthermore, stiffness-dependent changes in macrophage function, both in vitro and in response to subcutaneous implantation of biomaterials in vivo, require Piezo1. Finally, we show that positive feedback between Piezo1 and actin drives macrophage activation. Together, our studies reveal that Piezo1 is a mechanosensor of stiffness in macrophages, and that its activity modulates polarization responses.

Suggested Citation

  • Hamza Atcha & Amit Jairaman & Jesse R. Holt & Vijaykumar S. Meli & Raji R. Nagalla & Praveen Krishna Veerasubramanian & Kyle T. Brumm & Huy E. Lim & Shivashankar Othy & Michael D. Cahalan & Medha M. P, 2021. "Mechanically activated ion channel Piezo1 modulates macrophage polarization and stiffness sensing," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-23482-5
    DOI: 10.1038/s41467-021-23482-5
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    Cited by:

    1. Yang Li & Nan Li & Wei Liu & Aleksander Prominski & Seounghun Kang & Yahao Dai & Youdi Liu & Huawei Hu & Shinya Wai & Shilei Dai & Zhe Cheng & Qi Su & Ping Cheng & Chen Wei & Lihua Jin & Jeffrey A. Hu, 2023. "Achieving tissue-level softness on stretchable electronics through a generalizable soft interlayer design," Nature Communications, Nature, vol. 14(1), pages 1-10, December.

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