Physiological type I collagen organization induces the formation of a novel class of linear invadosomes

Mol Biol Cell. 2012 Jan;23(2):297-309. doi: 10.1091/mbc.E11-07-0594. Epub 2011 Nov 23.


Invadosomes are F-actin structures capable of degrading the matrix through the activation of matrix metalloproteases. As fibrillar type I collagen promotes pro-matrix metalloproteinase 2 activation by membrane type 1 matrix metalloproteinase, we aimed at investigating the functional relationships between collagen I organization and invadosome induction. We found that fibrillar collagen I induced linear F-actin structures, distributed along the fibrils, on endothelial cells, macrophages, fibroblasts, and tumor cells. These structures share features with conventional invadosomes, as they express cortactin and N-WASP and accumulate the scaffold protein Tks5, which proved essential for their formation. On the basis of their ability to degrade extracellular matrix elements and their original architecture, we named these structures "linear invadosomes." Interestingly, podosomes or invadopodia were replaced by linear invadosomes upon contact of the cells with fibrillar collagen I. However, linear invadosomes clearly differ from classical invadosomes, as they do not contain paxillin, vinculin, and β1/β3 integrins. Using knockout mouse embryonic fibroblasts and RGD peptide, we demonstrate that linear invadosome formation and activity are independent of β1 and β3 integrins. Finally, linear invadosomes also formed in a three-dimensional collagen matrix. This study demonstrates that fibrillar collagen I is the physiological inducer of a novel class of invadosomes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism
  • Adaptor Proteins, Vesicular Transport / metabolism
  • Animals
  • Cattle
  • Cell Line
  • Collagen Type I / metabolism*
  • Collagen Type I / ultrastructure*
  • Cricetinae
  • Extracellular Matrix / metabolism*
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism
  • Fibroblasts / ultrastructure
  • Humans
  • Integrin beta1 / metabolism
  • Integrin beta3 / metabolism
  • Mice
  • Mice, Knockout
  • Oligopeptides / pharmacology
  • Swine
  • Wiskott-Aldrich Syndrome Protein, Neuronal / metabolism


  • Actins
  • Adaptor Proteins, Vesicular Transport
  • Collagen Type I
  • Integrin beta1
  • Integrin beta3
  • Oligopeptides
  • SH3PXD2A protein, human
  • Wiskott-Aldrich Syndrome Protein, Neuronal
  • arginyl-glycyl-aspartic acid