WASp triggers mechanosensitive actin patches to facilitate immune cell migration in dense tissues

Dev Cell. 2022 Jan 10;57(1):47-62.e9. doi: 10.1016/j.devcel.2021.11.024. Epub 2021 Dec 16.


When crawling through the body, leukocytes often traverse tissues that are densely packed with extracellular matrix and other cells, and this raises the question: How do leukocytes overcome compressive mechanical loads? Here, we show that the actin cortex of leukocytes is mechanoresponsive and that this responsiveness requires neither force sensing via the nucleus nor adhesive interactions with a substrate. Upon global compression of the cell body as well as local indentation of the plasma membrane, Wiskott-Aldrich syndrome protein (WASp) assembles into dot-like structures, providing activation platforms for Arp2/3 nucleated actin patches. These patches locally push against the external load, which can be obstructing collagen fibers or other cells, and thereby create space to facilitate forward locomotion. We show in vitro and in vivo that this WASp function is rate limiting for ameboid leukocyte migration in dense but not in loose environments and is required for trafficking through diverse tissues such as skin and lymph nodes.

Keywords: T cells; Wiskott-Aldrich syndrome protein; actin cytoskeleton; ameboid motility; cell migration; confinement; dendritic cells; leukocytes; mechanical load; mechanosensing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actin-Related Protein 2-3 Complex / metabolism
  • Actin-Related Protein 2-3 Complex / physiology
  • Actin-Related Protein 3 / metabolism
  • Actins / metabolism
  • Actins / physiology*
  • Animals
  • Biomechanical Phenomena / physiology
  • Cell Line
  • Cell Movement / physiology
  • Cytoskeletal Proteins / metabolism
  • Female
  • Leukocytes / physiology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Protein Binding / physiology
  • Wiskott-Aldrich Syndrome Protein / genetics
  • Wiskott-Aldrich Syndrome Protein / metabolism*


  • Actin-Related Protein 2-3 Complex
  • Actin-Related Protein 3
  • Actins
  • Cytoskeletal Proteins
  • Wiskott-Aldrich Syndrome Protein