Collagen-based cell migration models in vitro and in vivo

Katarina Wolf, Stephanie Alexander, Vivien Schacht, Lisa M. Coussens, Ulrich H. von Andrian, Jacco van Rheenen, Elena Deryugina, Peter Friedl

Research output: Contribution to journalReview articlepeer-review

479 Scopus citations


Fibrillar collagen is the most abundant extracellular matrix (ECM) constituent which maintains the structure of most interstitial tissues and organs, including skin, gut, and breast. Density and spatial alignments of the three-dimensional (3D) collagen architecture define mechanical tissue properties, i.e. stiffness and porosity, which guide or oppose cell migration and positioning in different contexts, such as morphogenesis, regeneration, immune response, and cancer progression. To reproduce interstitial cell movement in vitro with high in vivo fidelity, 3D collagen lattices are being reconstituted from extracted collagen monomers, resulting in the re-assembly of a fibrillar meshwork of defined porosity and stiffness. With a focus on tumor invasion studies, we here evaluate different in vitro collagen-based cell invasion models, employing either pepsinized or non-pepsinized collagen extracts, and compare their structure to connective tissue in vivo, including mouse dermis and mammary gland, chick chorioallantoic membrane (CAM), and human dermis. Using confocal reflection and two-photon-excited second harmonic generation (SHG) microscopy, we here show that, depending on the collagen source, in vitro models yield homogeneous fibrillar texture with a quite narrow range of pore size variation, whereas all in vivo scaffolds comprise a range from low- to high-density fibrillar networks and heterogeneous pore sizes within the same tissue. Future in-depth comparison of structure and physical properties between 3D ECM-based models in vitro and in vivo are mandatory to better understand the mechanisms and limits of interstitial cell movements in distinct tissue environments.

Original languageEnglish (US)
Pages (from-to)931-941
Number of pages11
JournalSeminars in Cell and Developmental Biology
Issue number8
StatePublished - Oct 2009
Externally publishedYes


  • Cancer cell invasion models
  • Confocal reflection microscopy
  • Connective tissue geometry
  • Physical collagen spacing
  • Second harmonic generation microscopy

ASJC Scopus subject areas

  • Developmental Biology
  • Cell Biology


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