In injured tissues, the fibrin-fibronectin (FN) provisional matrix provides a framework for cell adhesion, migration, and repair. Effective repair and remodeling require a proper balance between extracellular matrix (ECM) deposition, contraction, and turnover. We utilized a three-dimensional (3D) fibrin-FN provisional matrix model to determine the contributions of the FN-binding integrin receptors α5β1 and α4β1 to matrix contraction. CHOα5 cells expressing α5β1, a receptor for FN's RGD cell-binding domain, were highly contractile, and cells were well spread on a 3D fibrin-FN matrix. In contrast, CHOα4 cells expressing the α4β1 receptor for FN's alternatively spliced V region attached less efficiently to FN and were deficient in fibrin-FN matrix contraction. Surprisingly, cell adhesion and matrix contraction by CHOα4 cells were dramatically enhanced, to levels equivalent to CHOα5 cells, when proteolyzed FN was used in place of intact FN in the fibrin-FN matrix. Similar enhancement was observed when ligand binding by α4β1 integrins was activated by treatment with Mn++, but not by stimulation of actin organization with LPA. Therefore, α4β1-dependent cell responses to the provisional matrix are modulated by cleavage of matrix components.
All Science Journal Classification (ASJC) codes
- Cell Biology
- Provisional matrix