Filamin A-beta1 integrin complex tunes epithelial cell response to matrix tension.

TitleFilamin A-beta1 integrin complex tunes epithelial cell response to matrix tension.
Publication TypeJournal Article
Year of Publication2009
AuthorsGehler S, Baldassarre M, Lad Y, Leight JL, Wozniak MA, Riching KM, Eliceiri KW, Weaver VM, Calderwood DA, Keely PJ
JournalMol Biol Cell
Date Published2009 Jul
KeywordsAnimals, Antigens, CD29, Biomechanical Phenomena, Cell Line, Tumor, Collagen, Contractile Proteins, Epithelial Cells, Extracellular Matrix, Filamins, Gels, Humans, Mice, Microfilament Proteins, Morphogenesis, Myosin Light Chains, Phosphorylation, Protein Binding

The physical properties of the extracellular matrix (ECM) regulate the behavior of several cell types; yet, mechanisms by which cells recognize and respond to changes in these properties are not clear. For example, breast epithelial cells undergo ductal morphogenesis only when cultured in a compliant collagen matrix, but not when the tension of the matrix is increased by loading collagen gels or by increasing collagen density. We report that the actin-binding protein filamin A (FLNa) is necessary for cells to contract collagen gels, and pull on collagen fibrils, which leads to collagen remodeling and morphogenesis in compliant, low-density gels. In stiffer, high-density gels, cells are not able to contract and remodel the matrix, and morphogenesis does not occur. However, increased FLNa-beta1 integrin interactions rescue gel contraction and remodeling in high-density gels, resulting in branching morphogenesis. These results suggest morphogenesis can be "tuned" by the balance between cell-generated contractility and opposing matrix stiffness. Our findings support a role for FLNa-beta1 integrin as a mechanosensitive complex that bidirectionally senses the tension of the matrix and, in turn, regulates cellular contractility and response to this matrix tension.

Alternate JournalMol. Biol. Cell
PubMed ID19458194
PubMed Central IDPMC2710838
Grant ListR01 CA-076537 / CA / NCI NIH HHS / United States
R01 CA142833 / CA / NCI NIH HHS / United States
R01 EB-000184 / EB / NIBIB NIH HHS / United States
R01 GM-068600 / GM / NIGMS NIH HHS / United States
T32 AG-20013 / AG / NIA NIH HHS / United States