Fibroblast morphogenesis on 3D collagen matrices: The balance between cell clustering and cell migration

Bruno da Rocha-Azevedo, Frederick Grinnell

Research output: Contribution to journalReview articlepeer-review

32 Scopus citations


Fibroblast clusters have been observed in tissues under a variety of circumstances: in fibrosis and scar, in the formation of hair follicle dermal papilla, and as part of the general process of mesenchymal condensation that takes place during development. Cell clustering has been shown to depend on features of the extracellular matrix, growth factor environment, and mechanisms to stabilize cell-cell interactions. In vitro studies have shown that increasing the potential for cell-cell adhesion relative to cell-substrate adhesion promotes cell clustering. Experimental models to study fibroblast clustering have utilized centrifugation, hanging drops, and substrata with poorly adhesive, soft and mechanically unstable properties. In this review, we summarize work on a new, highly tractable, cell clustering research model in which human fibroblasts are incubated on the surfaces of collagen matrices. Fibroblast clustering occurs under procontractile growth factor conditions (e.g., serum or the serum lipid agonist lysophosphatidic acid) but not under promigratory growth factor conditions (e.g., platelet-derived growth factor) and can be reversed by switching growth factor environments. Cell contraction plays a dual role in clustering to bring cells closer together and to stimulate cells to organize fibronectin into a fibrillar matrix. Binding of fibroblasts to a shared fibronectin fibrillar matrix stabilizes clusters, and fragmentation of the fibrillar matrix occurs when growth factor conditions are switched to promote cell dispersal.

Original languageEnglish (US)
Pages (from-to)2440-2446
Number of pages7
JournalExperimental Cell Research
Issue number16
StatePublished - Oct 1 2013


  • 3D-collagen matrix
  • Adherens junctions
  • Cell aggregation
  • Cell clustering
  • Cell contraction
  • Cell migration
  • Fibronectin
  • Tissue morphogenesis

ASJC Scopus subject areas

  • Cell Biology


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