Mechanically activated ion channel Piezo1 modulates macrophage polarization and stiffness sensing

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. Pathak and Wendy F. Liu ()
Additional contact information
Hamza Atcha: University of California Irvine
Amit Jairaman: University of California Irvine
Jesse R. Holt: University of California Irvine
Vijaykumar S. Meli: University of California Irvine
Raji R. Nagalla: University of California Irvine
Praveen Krishna Veerasubramanian: University of California Irvine
Kyle T. Brumm: University of California Irvine
Huy E. Lim: University of California Irvine
Shivashankar Othy: University of California Irvine
Michael D. Cahalan: University of California Irvine
Medha M. Pathak: University of California Irvine
Wendy F. Liu: University of California Irvine

Nature Communications, 2021, vol. 12, issue 1, 1-14

Abstract: 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.

Date: 2021
References: Add references at CitEc
Citations: View citations in EconPapers (3)

Downloads: (external link)
https://www.nature.com/articles/s41467-021-23482-5 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-23482-5

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-021-23482-5

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().