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Proc Natl Acad Sci U S A. 2020 Feb 4;117(5):2506-2512. doi: 10.1073/pnas.1905730117. Epub 2020 Jan 21.

Pressure sensing through Piezo channels controls whether cells migrate with blebs or pseudopods.

Author information

1
Department of Engineering, University of Cambridge, Cambridge CB2 1PZ, United Kingdom.
2
Institut Curie, Université Paris Sciences et Lettres, CNRS, UMR 144, 75005 Paris, France.
3
Institut Pierre-Gilles de Gennes, Université Paris Sciences et Lettres, 75005 Paris, France.
4
Laboratory of Molecular Biology, Medical Research Council, Cambridge CB20QH, United Kingdom.
5
Laboratory of Molecular Biology, Medical Research Council, Cambridge CB20QH, United Kingdom; rrk@mrc-lmb.cam.ac.uk.

Abstract

Blebs and pseudopods can both power cell migration, with blebs often favored in tissues, where cells encounter increased mechanical resistance. To investigate how migrating cells detect and respond to mechanical forces, we used a "cell squasher" to apply uniaxial pressure to Dictyostelium cells chemotaxing under soft agarose. As little as 100 Pa causes a rapid (<10 s), sustained shift to movement with blebs rather than pseudopods. Cells are flattened under load and lose volume; the actin cytoskeleton is reorganized, with myosin II recruited to the cortex, which may pressurize the cytoplasm for blebbing. The transition to bleb-driven motility requires extracellular calcium and is accompanied by increased cytosolic calcium. It is largely abrogated in cells lacking the Piezo stretch-operated channel; under load, these cells persist in using pseudopods and chemotax poorly. We propose that migrating cells sense pressure through Piezo, which mediates calcium influx, directing movement with blebs instead of pseudopods.

KEYWORDS:

Dictyostelium; Piezo; blebbing; cell migration; chemotaxis

PMID:
31964823
DOI:
10.1073/pnas.1905730117
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