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Quantitatively distinct requirements for signaling-competent cell spreading on engineered versus natural adhesion ligands

Richman, Gabriel P. and Tirrell, David A. and Asthagiri, Anand R. (2005) Quantitatively distinct requirements for signaling-competent cell spreading on engineered versus natural adhesion ligands. Journal of Controlled Release, 101 (1-3). pp. 3-12. ISSN 0168-3659. doi:10.1016/j.jconrel.2004.07.034.

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To design synthetic microenvironments that elicit desired cell behaviors, we must better understand the molecular mechanisms by which cells interact with candidate biomaterials. Using cell lines with distinct α5β1 integrin expression profiles, we demonstrate that this integrin mediates cell spreading on substrata coated with genetically engineered artificial extracellular matrix (aECM) proteins containing the RGD sequence (RGD-containing aECM protein [^aRGD]) but lacking the PHSRN synergy site. Furthermore, ^aRGD-mediated adhesion stimulates an intracellular focal adhesion kinase (FAK) signal that is indicative of integrin tethering. Although both ^aRGD and the natural ECM protein fibronectin (FN) support α5β1 integrin-mediated cell spreading, quantitative single-cell analysis revealed that aRGD-mediated spreading requires ten-fold greater threshold amount of integrin expression than FN-mediated spreading. Our analysis demonstrates that ^aRGD-based substrata mediate both biophysical (cell spreading) and biochemical (FAK signaling) events via the α5β1 integrin, albeit with efficacy quantitatively distinct from that of natural ECM proteins that possess the full spectrum of adhesion and synergy domains.

Item Type:Article
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Tirrell, David A.0000-0003-3175-4596
Additional Information:c2004 Elsevier B.V. Received 24 June 2004; accepted 7 July 2004; Available online 12 October 2004. The authors thank members of the A.R.A. and D.A.T. labs for helpful discussions and technical assistance. This work was funded by a start-up grant from California Institute of Technology to A.R.A. and NIH grant 5 R01 HL59987-03 to D.A.T. G.P.R. was partially funded by a graduate fellowship from the NSF-sponsored Materials Research Science and Engineering Center at California Institute of Technology.
Funding AgencyGrant Number
NIH5 R01 HL59987-03
Subject Keywords:Biomaterial; Extracellular matrix; Focal adhesion kinase; Integrin; RGD
Issue or Number:1-3
Record Number:CaltechAUTHORS:20150120-160852739
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:53903
Deposited By: Katherine Johnson
Deposited On:21 Jan 2015 00:18
Last Modified:10 Nov 2021 20:08

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