Accessibility to the fibronectin synergy site in a 3D matrix regulates engagement of α5β1 versus αvβ3 integrin receptors

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Abstract

Cell adhesion and migration on fibronectin (FN) extracellular matrix are mediated by integrin receptors. Integrins α5β1 and αvβ3 require the RGD cell-binding sequence in FN, but α5β1 also requires the nearby synergy site for maximal binding. In this study, we investigated how differences in the numbers of RGD or synergy sites within a three-dimensional (3D) FN-rich matrix influence cell adhesion and migration. CHO cell adhesion, spreading, and migration were reduced on 3D chimeric matrix containing FN lacking RGD (FN(RGD-)). Incorporation of FN with mutation of the synergy site (FN(syn-)), however, resulted in selective usage of integrins. CHO cells expressing α5β1 showed decreased interactions with FN(syn-) chimeric matrix. In contrast, the presence of FN(syn-) had no effect on CHOαvβ3 cell migration. Interestingly, CHOα5/ αvβ3 cells expressing both integrins selectively used α5β1 for migration on wild type FN matrix but preferred αvβ3 for migration on FN(syn-) chimeric matrix. Thus sequestration or exposure of the FN synergy site within a 3D matrix may represent a novel mechanism for regulating cell functions through differential usage of integrin receptors. [Supplementary materials are available for this article. Go to the publisher's online edition of Cell Communication and Adhesion for the following free supplemental resource: a video recording shows migration of HT1080 cells on 3D matrix. HT1080 cells were allowed to attach to the matrix in serum-free DMEM for 2 h. FBS was then added to the medium to a final concentration of 10% and video recording was started. Images were taken every 5 min for 2 h. The video plays at 6 frames/s].

Original languageEnglish (US)
Pages (from-to)267-277
Number of pages11
JournalCell Communication and Adhesion
Volume13
Issue number5-6
DOIs
StatePublished - Sep 1 2006

All Science Journal Classification (ASJC) codes

  • Clinical Biochemistry
  • Cell Biology

Keywords

  • 3D matrix
  • Fibronectin
  • Integrin
  • Migration
  • RGD

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