Title | Filamin A-beta1 integrin complex tunes epithelial cell response to matrix tension. |
Publication Type | Journal Article |
Year of Publication | 2009 |
Authors | Gehler S, Baldassarre M, Lad Y, Leight JL, Wozniak MA, Riching KM, Eliceiri KW, Weaver VM, Calderwood DA, Keely PJ |
Journal | Mol Biol Cell |
Volume | 20 |
Issue | 14 |
Pagination | 3224-38 |
Date Published | 2009 Jul |
ISSN | 1939-4586 |
Keywords | Animals, 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 |
Abstract | 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. |
DOI | 10.1091/mbc.E08-12-1186 |
Alternate Journal | Mol. Biol. Cell |
PubMed ID | 19458194 |
PubMed Central ID | PMC2710838 |
Grant List | R01 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 |