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nature portfolio nuclear factor kappa-light-chain-enhancer privacy policy ix3-zdc2 z-drift compensator open-source image processing advertising ifnγ/lps-induced ca2+ activity suppresses il4/il13-induced activation il4/il13-induced stat6 activation nf-κb signaling pathway reduced ifnγ/lps-induced inflammatory elisa kits il4/il13-stimulated bmdms deficient nature 515 nature 573 nature cardiovascular applied research cytokine-mediated macrophage activation solutions reprints stretch-activated cation channel transcription factor nf-kappa supplementary information files generate lsl-salsa6f-vav1cre/+ mice piezo-1–mediated monocyte activation internal cell-generated forces stretch-activated ion channels incomplete sirna-mediated knockdown trpv4 calcium-permeable channel il4/il13-induced arg1 author information authors research shows research design yoda1-induced channel activation trpc1-mediated calcium entry piezo1-mediated macrophage activation high-speed resonance scanner experimental autoimmune cystitis piezo1-mediated ca2+ influx mechanotransduction channel piezo1 1 ng/ml il4/il13 ifnγ/lps-stimulated bmdms cultured analyze macrophage-specific phenotypes exact p-values significantly enhanced f-actin stiffness-mediated macrophage activation activity enhances ifnγ/lps reporting summary central nervous system enzyme-free dissociation buffer

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         headline:Mechanically activated ion channel Piezo1 modulates macrophage polarization and stiffness sensing
         description: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. Macrophages perform diverse functions during immune responses, but the molecular mechanisms by which physical properties of the tissue regulate macrophage behavior remain unknown. Here the authors find that Piezo1 is a mechanosensor of stiffness, and that its activity modulates macrophage polarization responses.
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      headline:Mechanically activated ion channel Piezo1 modulates macrophage polarization and stiffness sensing
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         name:The Edwards Lifesciences Center for Advanced Cardiovascular Technology, University of California Irvine, Irvine, USA
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            address:
               name:Department of Physiology and Biophysics, University of California Irvine, Irvine, USA
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            name:University of California Irvine
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            name:University of California Irvine
            address:
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            name:University of California Irvine
            address:
               name:The Edwards Lifesciences Center for Advanced Cardiovascular Technology, University of California Irvine, Irvine, USA
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            address:
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               type:PostalAddress
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            name:University of California Irvine
            address:
               name:The Edwards Lifesciences Center for Advanced Cardiovascular Technology, University of California Irvine, Irvine, USA
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            address:
               name:Department of Physiology and Biophysics, University of California Irvine, Irvine, USA
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      name:Michael D. Cahalan
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            address:
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            address:
               name:Department of Biomedical Engineering, University of California Irvine, Irvine, USA
               type:PostalAddress
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            name:University of California Irvine
            address:
               name:Department of Physiology and Biophysics, University of California Irvine, Irvine, USA
               type:PostalAddress
            type:Organization
            name:University of California Irvine
            address:
               name:Sue and Bill Gross Stem Cell Research Center, University of California Irvine, Irvine, USA
               type:PostalAddress
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      name:Wendy F. Liu
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      affiliation:
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            address:
               name:Department of Biomedical Engineering, University of California Irvine, Irvine, USA
               type:PostalAddress
            type:Organization
            name:University of California Irvine
            address:
               name:The Edwards Lifesciences Center for Advanced Cardiovascular Technology, University of California Irvine, Irvine, USA
               type:PostalAddress
            type:Organization
            name:University of California Irvine
            address:
               name:Department of Chemical and Biomolecular Engineering, University of California Irvine, Irvine, USA
               type:PostalAddress
            type:Organization
      email:[email protected]
PostalAddress:
      name:Department of Biomedical Engineering, University of California Irvine, Irvine, USA
      name:The Edwards Lifesciences Center for Advanced Cardiovascular Technology, University of California Irvine, Irvine, USA
      name:Department of Physiology and Biophysics, University of California Irvine, Irvine, USA
      name:Department of Physiology and Biophysics, University of California Irvine, Irvine, USA
      name:Sue and Bill Gross Stem Cell Research Center, University of California Irvine, Irvine, USA
      name:Department of Biomedical Engineering, University of California Irvine, Irvine, USA
      name:The Edwards Lifesciences Center for Advanced Cardiovascular Technology, University of California Irvine, Irvine, USA
      name:Department of Chemical and Biomolecular Engineering, University of California Irvine, Irvine, USA
      name:Department of Biomedical Engineering, University of California Irvine, Irvine, USA
      name:The Edwards Lifesciences Center for Advanced Cardiovascular Technology, University of California Irvine, Irvine, USA
      name:Department of Biomedical Engineering, University of California Irvine, Irvine, USA
      name:The Edwards Lifesciences Center for Advanced Cardiovascular Technology, University of California Irvine, Irvine, USA
      name:Department of Biomedical Engineering, University of California Irvine, Irvine, USA
      name:The Edwards Lifesciences Center for Advanced Cardiovascular Technology, University of California Irvine, Irvine, USA
      name:Department of Biomedical Engineering, University of California Irvine, Irvine, USA
      name:The Edwards Lifesciences Center for Advanced Cardiovascular Technology, University of California Irvine, Irvine, USA
      name:Department of Physiology and Biophysics, University of California Irvine, Irvine, USA
      name:Department of Physiology and Biophysics, University of California Irvine, Irvine, USA
      name:Department of Biomedical Engineering, University of California Irvine, Irvine, USA
      name:Department of Physiology and Biophysics, University of California Irvine, Irvine, USA
      name:Sue and Bill Gross Stem Cell Research Center, University of California Irvine, Irvine, USA
      name:Department of Biomedical Engineering, University of California Irvine, Irvine, USA
      name:The Edwards Lifesciences Center for Advanced Cardiovascular Technology, University of California Irvine, Irvine, USA
      name:Department of Chemical and Biomolecular Engineering, University of California Irvine, Irvine, USA

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