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Endothelial cell adhesion to the fibronectin CS5 domain in artificial extracellular matrix proteins

Heilshorn, Sarah C. and DiZio, Kathleen A. and Welsh, Eric R. and Tirrell, David A. (2003) Endothelial cell adhesion to the fibronectin CS5 domain in artificial extracellular matrix proteins. Biomaterials, 24 (23). pp. 4245-4252. ISSN 0142-9612. doi:10.1016/S0142-9612(03)00294-1.

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This study examines the spreading and adhesion of human umbilical vein endothelial cells (HUVEC) on artificial extracellular matrix (aECM) proteins containing sequences derived from elastin and fibronectin. Three aECM variants were studied: aECM 1 contains lysine residues periodically spaced within the protein sequence and three repeats of the CS5 domain of fibronectin, aECM 2 contains periodically spaced lysines and three repeats of a scrambled CS5 sequence, and aECM 3 contains lysines at the protein termini and five CS5 repeats. Comparative cell binding and peptide inhibition assays confirm that the tetrapeptide sequence REDV is responsible for HUVEC adhesion to aECM proteins that contain the CS5 domain. Furthermore, more than 60% of adherent HUVEC were retained on aECM 1 after exposure to physiologically relevant shear stresses (⩽100 dynes/cm^2). Finally, the levels of thrombogenic markers (tissue plasminogen activator and plasminogen activator inhibitor–1) secreted by HUVEC monolayers on aECM 1 were found to be similar to those secreted by HUVEC monolayers cultured on fibronectin. These characteristics, along with the physical strength and elasticity of crosslinked films prepared from these materials, make aECM proteins promising candidates for application in small-diameter vascular grafts.

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Tirrell, David A.0000-0003-3175-4596
Additional Information:© 2003 Elsevier Ltd. Received 16 December 2002; accepted 8 April 2003. Acknowledgements: We thank Paul Nowatzki for expression and purification of aECM 3, Krystle Wang and Summer Zhang for help with the lipopolysaccharide assays, Sarah Wilhoit and Michelle Giron for help with the competitive inhibition binding assays, and Julie Liu for helpful discussions. Funding was provided by the National Institutes of Health and the National Science Foundation.
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Subject Keywords:Cell adhesion; Endothelial cell; Extracellular matrix; Protein design; Vascular graft
Issue or Number:23
Record Number:CaltechAUTHORS:20150123-160702434
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:54039
Deposited By: Katherine Johnson
Deposited On:24 Jan 2015 00:13
Last Modified:10 Nov 2021 20:26

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