期刊
MOLECULAR BIOLOGY OF THE CELL
卷 20, 期 14, 页码 3224-3238出版社
AMER SOC CELL BIOLOGY
DOI: 10.1091/mbc.E08-12-1186
关键词
-
类别
资金
- National Institutes of Health [R01 GM-068600]
- National Institute on Aging [T32 AG-20013]
- National Cancer Institute [R01CA-076537]
- National Institutes of Health National Institute of Biomedical Imaging and Bioengineering [R01 EB-000184]
- American Cancer Society [RSG-00-339-04]
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-beta 1 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-beta 1 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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据