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Measurement of the Interaction Between Recombinant I-domain from Integrin alpha 2 beta 1 and a Triple Helical Collagen Peptide with the GFOGER Binding Motif Using Molecular Force Spectroscopy

The role of the collagen-platelet interaction is of crucial importance to the haemostatic response during both injury and pathogenesis of the blood vessel wall. Of particular interest is the high affinity interaction of the platelet transmembrane receptor, alpha 2 beta 1, responsible for firm attach...

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Autores principales: Attwood, Simon J., Simpson, Anna M. C., Hamaia, SamirW., Bihan, Dominique, Roy, Debdulal, Farndale, RichardW., Welland, Mark E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3588017/
https://www.ncbi.nlm.nih.gov/pubmed/23434650
http://dx.doi.org/10.3390/ijms14022832
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author Attwood, Simon J.
Simpson, Anna M. C.
Hamaia, SamirW.
Bihan, Dominique
Roy, Debdulal
Farndale, RichardW.
Welland, Mark E.
author_facet Attwood, Simon J.
Simpson, Anna M. C.
Hamaia, SamirW.
Bihan, Dominique
Roy, Debdulal
Farndale, RichardW.
Welland, Mark E.
author_sort Attwood, Simon J.
collection PubMed
description The role of the collagen-platelet interaction is of crucial importance to the haemostatic response during both injury and pathogenesis of the blood vessel wall. Of particular interest is the high affinity interaction of the platelet transmembrane receptor, alpha 2 beta 1, responsible for firm attachment of platelets to collagen at and around injury sites. We employ single molecule force spectroscopy (SMFS) using the atomic force microscope (AFM) to study the interaction of the I-domain from integrin alpha 2 beta 1 with a synthetic collagen related triple-helical peptide containing the high-affinity integrin-binding GFOGER motif, and a control peptide lacking this sequence, referred to as GPP. By utilising synthetic peptides in this manner we are able to study at the molecular level subtleties that would otherwise be lost when considering cell-to-collagen matrix interactions using ensemble techniques. We demonstrate for the first time the complexity of this interaction as illustrated by the complex multi-peaked force spectra and confirm specificity using control blocking experiments. In addition we observe specific interaction of the GPP peptide sequence with the I-domain. We propose a model to explain these observations.
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spelling pubmed-35880172013-03-13 Measurement of the Interaction Between Recombinant I-domain from Integrin alpha 2 beta 1 and a Triple Helical Collagen Peptide with the GFOGER Binding Motif Using Molecular Force Spectroscopy Attwood, Simon J. Simpson, Anna M. C. Hamaia, SamirW. Bihan, Dominique Roy, Debdulal Farndale, RichardW. Welland, Mark E. Int J Mol Sci Article The role of the collagen-platelet interaction is of crucial importance to the haemostatic response during both injury and pathogenesis of the blood vessel wall. Of particular interest is the high affinity interaction of the platelet transmembrane receptor, alpha 2 beta 1, responsible for firm attachment of platelets to collagen at and around injury sites. We employ single molecule force spectroscopy (SMFS) using the atomic force microscope (AFM) to study the interaction of the I-domain from integrin alpha 2 beta 1 with a synthetic collagen related triple-helical peptide containing the high-affinity integrin-binding GFOGER motif, and a control peptide lacking this sequence, referred to as GPP. By utilising synthetic peptides in this manner we are able to study at the molecular level subtleties that would otherwise be lost when considering cell-to-collagen matrix interactions using ensemble techniques. We demonstrate for the first time the complexity of this interaction as illustrated by the complex multi-peaked force spectra and confirm specificity using control blocking experiments. In addition we observe specific interaction of the GPP peptide sequence with the I-domain. We propose a model to explain these observations. MDPI 2013-01-29 /pmc/articles/PMC3588017/ /pubmed/23434650 http://dx.doi.org/10.3390/ijms14022832 Text en © 2013 by the authors; licensee Molecular Diversity Preservation International, Basel, Switzerland. http://creativecommons.org/licenses/by/3.0 This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).
spellingShingle Article
Attwood, Simon J.
Simpson, Anna M. C.
Hamaia, SamirW.
Bihan, Dominique
Roy, Debdulal
Farndale, RichardW.
Welland, Mark E.
Measurement of the Interaction Between Recombinant I-domain from Integrin alpha 2 beta 1 and a Triple Helical Collagen Peptide with the GFOGER Binding Motif Using Molecular Force Spectroscopy
title Measurement of the Interaction Between Recombinant I-domain from Integrin alpha 2 beta 1 and a Triple Helical Collagen Peptide with the GFOGER Binding Motif Using Molecular Force Spectroscopy
title_full Measurement of the Interaction Between Recombinant I-domain from Integrin alpha 2 beta 1 and a Triple Helical Collagen Peptide with the GFOGER Binding Motif Using Molecular Force Spectroscopy
title_fullStr Measurement of the Interaction Between Recombinant I-domain from Integrin alpha 2 beta 1 and a Triple Helical Collagen Peptide with the GFOGER Binding Motif Using Molecular Force Spectroscopy
title_full_unstemmed Measurement of the Interaction Between Recombinant I-domain from Integrin alpha 2 beta 1 and a Triple Helical Collagen Peptide with the GFOGER Binding Motif Using Molecular Force Spectroscopy
title_short Measurement of the Interaction Between Recombinant I-domain from Integrin alpha 2 beta 1 and a Triple Helical Collagen Peptide with the GFOGER Binding Motif Using Molecular Force Spectroscopy
title_sort measurement of the interaction between recombinant i-domain from integrin alpha 2 beta 1 and a triple helical collagen peptide with the gfoger binding motif using molecular force spectroscopy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3588017/
https://www.ncbi.nlm.nih.gov/pubmed/23434650
http://dx.doi.org/10.3390/ijms14022832
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