TY - JOUR
T1 - Fibroblast morphogenesis on 3D collagen matrices
T2 - The balance between cell clustering and cell migration
AU - da Rocha-Azevedo, Bruno
AU - Grinnell, Frederick
N1 - Funding Information:
Thanks to Chin-Han Ho and Zhenan Liu for helpful comments. Research in our laboratory is supported by NIH Grant GM031321 . This work was performed in laboratories constructed with support from NIH Grant C06-RR30414 .
PY - 2013/10/1
Y1 - 2013/10/1
N2 - 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.
AB - 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.
KW - 3D-collagen matrix
KW - Adherens junctions
KW - Cell aggregation
KW - Cell clustering
KW - Cell contraction
KW - Cell migration
KW - Fibronectin
KW - Tissue morphogenesis
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U2 - 10.1016/j.yexcr.2013.05.003
DO - 10.1016/j.yexcr.2013.05.003
M3 - Review article
C2 - 23664837
AN - SCOPUS:84883552306
SN - 0014-4827
VL - 319
SP - 2440
EP - 2446
JO - Experimental Cell Research
JF - Experimental Cell Research
IS - 16
ER -