Journal
ANNALS OF BIOMEDICAL ENGINEERING
Volume 39, Issue 7, Pages 1849-1856Publisher
SPRINGER
DOI: 10.1007/s10439-011-0310-9
Keywords
Endothelial cells; Cell mechanics; Substrate stiffness; Fibronectin
Categories
Funding
- National Institutes of Health
- National Science Foundation
- American Heart Association
- American Federation for Aging Research
- Cornell Nanobiotechnology Center
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The mechanism by which cells organize into tissues is fundamental to developmental biology and tissue engineering. Likewise, the disruption of cellular order within tissues is a hallmark of many diseases including cancer and atherosclerosis. Tissue formation is regulated, in part, by a balance between cell-cell cohesion and cell-extracellular matrix (ECM) adhesion. Here, experiments and approaches to alter this balance are discussed, and the nature of this balance in the formation of microvasculature is explored. Using matrices of tailored stiffness and matrix presentation, the role of the mechanical properties and ligand density in angiogenesis has been investigated. Decreasing cell-matrix adhesion by either reducing matrix stiffness or matrix ligand density induces the self-assembly of endothelial cells into network-like structures. These structures are stabilized by the polymerization of the extracellular matrix protein fibronectin. When fibronectin polymerization is inhibited, network formation does not occur. Interestingly, this interplay between substrate mechanics, ECM assembly, and tissue self-assembly is not limited to endothelial cells and has been observed in other cell types as well. These results suggest novel approaches to foster stable cell-cell adhesion and engineer tissues.
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