Tissue development and function depend upon a complex and dynamic interplay between cells and their surrounding extracellular matrix. Adhesion of cells to extracellular matrix proteins via specific cell surface receptors initiates intracellular signaling events that regulate many key aspects of cell behavior. Moreover, the precise composition and organization of the extracellular matrix contribute to the mechanical and permeability properties of the skin, vasculature, lungs, and other organs. In particular, the mechanical properties of load-bearing tissues, including blood vessels and cardiac muscle, are critical to their performance in the body. Hence, successful approaches to tissue engineering require not only an understanding of how cells interact with and organize extracellular matrix proteins into a complex, three-dimensional structure, but also an understanding of how these events subsequently contribute to the mechanical properties of artificial tissue constructs. Both the actin cytoskeleton and the extracellular matrix contribute quantitatively to the mechanical properties of artificial tissues. Our data indicate that the polymerization of fibronectin into the extracellular matrix plays a unique role in regulating both cytoskeletal tension generation and extracellular matrix organization. Our preliminary studies also indicate that the addition of fibronectin to cell-populated collagen lattices increases the toughness and ultimate strength of these biogels. In this proposal, we will determine how the polymerization and subsequent stabilization of fibronectin into the extracellular matrix contributes to the tensile mechanical properties of an established tissue model. Quantitatively determining how matrix fibronectin affects the tensile properties of collagen-based biogels will provide essential information that ultimately may be used to molecularly tailor extracellular matrices to enhance the performance of load-bearing tissue constructs.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21EB000986-02
Application #
6656859
Study Section
Special Emphasis Panel (ZHL1-CSR-O (S1))
Program Officer
Kelley, Christine A
Project Start
2002-09-10
Project End
2005-08-31
Budget Start
2003-09-01
Budget End
2004-08-31
Support Year
2
Fiscal Year
2003
Total Cost
$236,250
Indirect Cost
Name
University of Rochester
Department
Pharmacology
Type
Schools of Dentistry
DUNS #
041294109
City
Rochester
State
NY
Country
United States
Zip Code
14627
Gui, Liqiong; Wojciechowski, Katherine; Gildner, Candace D et al. (2006) Identification of the heparin-binding determinants within fibronectin repeat III1: role in cell spreading and growth. J Biol Chem 281:34816-25
Wojciechowski, Katherine; Chang, Cecilia H; Hocking, Denise C (2004) Expression, production, and characterization of full-length vitronectin in Escherichia coli. Protein Expr Purif 36:131-8
Gildner, Candace D; Lerner, Amy L; Hocking, Denise C (2004) Fibronectin matrix polymerization increases tensile strength of model tissue. Am J Physiol Heart Circ Physiol 287:H46-53