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Fibronectin fibrillogenesis regulates three-dimensional neovessel formation
Xiaoming Zhou1, R Grant Rowe, Nobuaki Hiraoka
1The Division of Molecular Medicine and Genetics, Department of Internal Medicine, The Life Sciences Institute, University of Michigan, Ann Arbor, Michigan 48109, USA.
Genes & Development
|May 3, 2008
Summary
Endothelial cells remodel fibronectin (Fn) into a fibrillar network, creating a scaffold that supports cytoskeletal organization and mechanical tension for new blood vessel formation. This process is crucial for neovascularization in three-dimensional (3D) environments.
Area of Science:
- Cell Biology
- Biomaterials Science
- Vascular Biology
Background:
- Endothelial cell behavior during blood vessel formation is influenced by the extracellular matrix (ECM).
- The remodeling of randomly ordered ECMs by endothelial cells to support neovascularization remains poorly understood.
Purpose of the Study:
- To investigate how endothelial cells remodel the three-dimensional (3D) extracellular matrix to support neovascularization.
- To elucidate the role of fibronectin (Fn) in endothelial cell responses within a 3D matrix.
Main Methods:
- Utilized 3D culture models with endothelial cells embedded in ECM components.
- Analyzed endothelial cell interactions with fibronectin, including unfolding and fibril deposition.
- Assessed the impact of fibronectin remodeling on cytoskeletal organization, cell tension, and viscoelasticity.
Main Results:
- Endothelial cells actively unfold soluble fibronectin (Fn) and deposit it as a pericellular fibrillar network.
- This Fn network supports endothelial cell cytoskeletal organization and actomyosin-dependent tension in a 3D-specific manner.
- The remodeled Fn matrix provides optimal viscoelastic properties for embedded cells.
Conclusions:
- Fibronectin polymerization by endothelial cells creates a structural scaffold essential for neovascularization.
- This scaffold displays adhesive ligands on a mechanically optimized substratum, promoting new blood vessel development.
- Fn remodeling is a key mechanism by which endothelial cells adapt to and modify their 3D microenvironment for angiogenesis.
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