Collagen fibrillogenesis: fibronectin, integrins, and minor collagens as organizers and nucleators

Curr Opin Cell Biol. 2008 Oct;20(5):495-501. doi: 10.1016/ Epub 2008 Jul 30.


Collagens are triple helical proteins that occur in the extracellular matrix (ECM) and at the cell-ECM interface. There are more than 30 collagens and collagen-related proteins but the most abundant are collagens I and II that exist as D-periodic (where D = 67 nm) fibrils. The fibrils are of broad biomedical importance and have central roles in embryogenesis, arthritis, tissue repair, fibrosis, tumor invasion, and cardiovascular disease. Collagens I and II spontaneously form fibrils in vitro, which shows that collagen fibrillogenesis is a selfassembly process. However, the situation in vivo is not that simple; collagen I-containing fibrils do not form in the absence of fibronectin, fibronectin-binding and collagen-binding integrins, and collagen V. Likewise, the thin collagen II-containing fibrils in cartilage do not form in the absence of collagen XI. Thus, in vivo, cellular mechanisms are in place to control what is otherwise a protein self-assembly process. This review puts forward a working hypothesis for how fibronectin and integrins (the organizers) determine the site of fibril assembly, and collagens V and XI (the nucleators) initiate collagen fibrillogenesis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cell Membrane / metabolism
  • Collagen / chemistry
  • Collagen / metabolism*
  • Extracellular Matrix / chemistry
  • Extracellular Matrix / metabolism
  • Fibronectins / metabolism*
  • Humans
  • Integrins / metabolism*
  • Models, Molecular
  • Protein Isoforms / chemistry
  • Protein Isoforms / metabolism*


  • Fibronectins
  • Integrins
  • Protein Isoforms
  • Collagen