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.
Original language | English |
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Pages (from-to) | 3224-3238 |
Number of pages | 15 |
Journal | Molecular Biology of the Cell |
Volume | 20 |
Issue number | 14 |
Early online date | 20 May 2009 |
DOIs | |
Publication status | Published - 15 Jul 2009 |
Keywords
- animals
- antigens, CD29
- biomechanics
- cell line, tumor
- collagen
- contractile proteins
- epithelial cells
- extracellular matrix
- gels
- humans
- mice
- microfilament proteins
- morphogenesis
- myosin light chains
- phosphorylation
- protein binding