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Three-dimensional Migration of Neurites Is Mediated by Adhesion Site Density and Affinity

Schense, Jason C. and Hubbell, Jeffrey A. (2000) Three-dimensional Migration of Neurites Is Mediated by Adhesion Site Density and Affinity. Journal of Biological Chemistry, 275 (10). pp. 6813-6818. ISSN 0021-9258.

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Three-dimensional neurite outgrowth rates within fibrin matrices that contained variable amounts of RGD peptides were shown to depend on adhesion site density and affinity. Bi-domain peptides with a factor XIIIa substrate in one domain and a RGD sequence in the other domain were covalently incorporated into fibrin gels during coagulation through the action of the transglutaminase factor XIIIa, and the RGD-dependent effect on neurite outgrowth was quantified, employing chick dorsal root ganglia cultured two- and three-dimensionally within the modified fibrin. Two separate bi-domain peptides were synthesized, one with a lower binding affinity linear RGD domain and another with a higher binding affinity cyclic RGD domain. Both peptides were cross-linked into fibrin gels at concentrations up to 8.2 mol of peptide/mol of fibrinogen, and their effect on neurite outgrowth was measured. Both two- and three-dimensional neurite outgrowth demonstrated a bi-phasic dependence on RGD concentration for both the linear and cyclic peptide, with intermediate adhesion site densities yielding maximal neurite extension and higher densities inhibiting outgrowth. The adhesion site density that yielded maximal outgrowth depended strongly on adhesion site affinity in both two and three dimensions, with lower densities of the higher affinity ligand being required (0.8-1.7 mol/mol for the linear peptide versus 0.2 mol/mol for the cyclic peptide yielding maximum neurite outgrowth rates in three-dimensional cultures).

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Additional Information:Copyright © 2000 by The American Society for Biochemistry and Molecular Biology, Inc. (Received for publication, October 19, 1999) We thank Dr. M. Höchli and Prof. T. Bächi of the Electronmicroscopical Laboratory at the University of Zurich for their assistance with confocal scanning laser microscopy. This work was funded by Grant 31-52261 NFP 38 from the Swiss National Science Foundation and a gift from F. Hoffmann-La Roche AG and Novartis Pharma AG. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Issue or Number:10
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:10015
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Deposited On:05 Apr 2008
Last Modified:03 Oct 2019 00:05

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