Self-organized podosomes are dynamic mechanosensors

Curr Biol. 2008 Sep 9;18(17):1288-94. doi: 10.1016/j.cub.2008.07.046. Epub 2008 Aug 28.


Podosomes are self-organized, dynamic, actin-containing structures that adhere to the extracellular matrix via integrins [1-5]. Yet, it is not clear what regulates podosome dynamics and whether podosomes can function as direct mechanosensors, like focal adhesions [6-9]. We show here that myosin-II proteins form circular structures outside and at the podosome actin ring to regulate podosome dynamics. Inhibiting myosin-II-dependent tension dissipated podosome actin rings before dissipating the myosin-ring structure. As podosome rings changed size or shape, tractions underneath the podosomes were exerted onto the substrate and were abolished when myosin-light-chain activity was inhibited. The magnitudes of tractions were comparable to those generated underneath focal adhesions, and they increased with substrate stiffness. The dynamics of podosomes and of focal adhesions were different. Torsional tractions underneath the podosome rings were generated with rotations of podosome rings in a nonmotile, nonrotating cell, suggesting a unique feature of these circular structures. Stresses applied via integrins at the apical surface directly displaced podosomes near the basal surface. Stress-induced podosome displacements increased nonlinearly with applied stresses. Our results suggest that podosomes are dynamic mechanosensors in which interactions of myosin tension and actin dynamics are crucial for regulating these self-organized structures in living cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actin Cytoskeleton / metabolism
  • Actin Cytoskeleton / physiology*
  • Actin Cytoskeleton / ultrastructure
  • Actins / metabolism
  • Actins / ultrastructure
  • Azepines / pharmacology
  • Cells, Cultured
  • Depsipeptides / pharmacology
  • Enzyme Inhibitors / pharmacology
  • Extracellular Matrix / drug effects
  • Extracellular Matrix / metabolism*
  • Extracellular Matrix / ultrastructure
  • Focal Adhesions / metabolism
  • Focal Adhesions / ultrastructure
  • Heterocyclic Compounds, 4 or More Rings / pharmacology
  • Integrins / metabolism
  • Mechanotransduction, Cellular / physiology*
  • Myosin Type II / antagonists & inhibitors
  • Myosin Type II / metabolism*
  • Myosin Type II / physiology
  • Myosin-Light-Chain Kinase / antagonists & inhibitors
  • Naphthalenes / pharmacology


  • Actins
  • Azepines
  • Depsipeptides
  • Enzyme Inhibitors
  • Heterocyclic Compounds, 4 or More Rings
  • Integrins
  • Naphthalenes
  • jasplakinolide
  • ML 7
  • blebbistatin
  • Myosin-Light-Chain Kinase
  • Myosin Type II