Modular actin nano-architecture enables podosome protrusion and mechanosensing

Nat Commun. 2019 Nov 15;10(1):5171. doi: 10.1038/s41467-019-13123-3.


Basement membrane transmigration during embryonal development, tissue homeostasis and tumor invasion relies on invadosomes, a collective term for invadopodia and podosomes. An adequate structural framework for this process is still missing. Here, we reveal the modular actin nano-architecture that enables podosome protrusion and mechanosensing. The podosome protrusive core contains a central branched actin module encased by a linear actin module, each harboring specific actin interactors and actin isoforms. From the core, two actin modules radiate: ventral filaments bound by vinculin and connected to the plasma membrane and dorsal interpodosomal filaments crosslinked by myosin IIA. On stiff substrates, the actin modules mediate long-range substrate exploration, associated with degradative behavior. On compliant substrates, the vinculin-bound ventral actin filaments shorten, resulting in short-range connectivity and a focally protrusive, non-degradative state. Our findings redefine podosome nanoscale architecture and reveal a paradigm for how actin modularity drives invadosome mechanosensing in cells that breach tissue boundaries.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / chemistry*
  • Actins / genetics
  • Actins / metabolism*
  • Animals
  • Cell Adhesion
  • Cell Membrane / genetics
  • Cell Membrane / metabolism
  • Cell Movement
  • Cells, Cultured
  • Dendritic Cells / chemistry
  • Dendritic Cells / cytology
  • Dendritic Cells / metabolism
  • Humans
  • Mechanotransduction, Cellular
  • Mice
  • Podosomes / chemistry
  • Podosomes / genetics
  • Podosomes / metabolism*


  • Actins