Skip to main content

Advertisement

SpringerLink
Log in

Surface plasmon resonance imaging coupled to on-chip mass spectrometry: a new tool to probe protein-GAG interactions

  • Research Paper
  • Published:
Analytical and Bioanalytical Chemistry Aims and scope Submit manuscript

Abstract

A biosensor device for the detection and characterization of protein-glycosaminoglycan interactions is being actively sought and constitutes the key to identifying specific carbohydrate ligands, an important issue in glycoscience. Mass spectrometry (MS) hyphenated methods are promising approaches for carbohydrate enrichment and subsequent structural characterization. In the study herein, we report the analysis of interactions between the glycosaminoglycans (GAGs) heparin (HP) and heparan sulfate (HS) and various cytokines by coupling surface plasmon resonance imaging (SPRi) for thermodynamic analysis method and MALDI-TOF MS for structural determination. To do so, we developed an SPR biochip in a microarray format and functionalized it with a self-assembled monolayer of short poly(ethylene oxide) chains for grafting the human cytokines stromal cell-derived factor-1 (SDF-1α), monocyte chemotactic protein-1 (MCP-1), and interferon-γ. The thermodynamic parameters of the interactions between these cytokines and unfractionated HP/HS and derived oligosaccharides were successively determined using SPRi monitoring, and the identification of the captured carbohydrates was carried out directly on the biochip surface using MALDI-TOF MS, revealing cytokine preferential affinity for GAGs. The MS identification was enhanced by on-chip digestion of the cytokine-bound GAGs with heparinase, leading to the detection of oligosaccharides likely involved in the binding sequence of GAG ligands. Although several carbohydrate array-based assays have been reported, this study is the first report of the successful analysis of protein-GAG interactions using SPRi-MS coupling.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  1. Bishop JR, Schuksz M, Esko JD. Heparan sulphate proteoglycans fine-tune mammalian physiology. Nature. 2007;446:1030–7.

    CAS  PubMed  Google Scholar 

  2. Linhardt RJ, Toida T. Role of glycosaminoglycans in cellular communication. Acc Chem Res. 2004;37:431–8.

    CAS  PubMed  Google Scholar 

  3. Sasisekharan R, Raman R, Prabhakar V. Glycomics approach to structure-function relationships of glycosaminoglycans. Annu Rev Biomed Eng. 2006;8:181–31.

    CAS  PubMed  Google Scholar 

  4. Capila I, Linhardt RJ. Heparin–protein interactions. Angew Chem Int Ed. 2002;41:390–12.

    CAS  Google Scholar 

  5. Spillmann D, Lindahl U. Glycosaminoglycan-protein interactions: a question of specificity. Curr Opin Struct Biol. 1994;4:677–82.

    CAS  Google Scholar 

  6. Ricard-Blum S. Protein–glycosaminoglycan interaction networks: focus on heparan sulfate. Perspect Sci. 2017;11:62–9.

    Google Scholar 

  7. Rogers CJ, Clark PM, Tully SE, Abrol R, Garcia KC, Goddard WA 3rd, et al. Elucidating glycosaminoglycan-protein-protein interactions using carbohydrate microarray and computational approaches. Proc Natl Acad Sci U S A. 2011;108:9747–52.

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Saesen E, Sarrazin S, Laguri C, Sadir R, Maurin D, Thomas A, et al. Insights into the mechanism by which interferon-γ basic amino acid clusters mediate protein binding to heparan sulfate. J Am Chem Soc. 2013;135:9384–90.

    CAS  PubMed  Google Scholar 

  9. Soares da Costa D, Reis RL, Pashkuleva I. Sulfation of glycosaminoglycans and its implications in human health and disorders. Annu Rev Biomed Eng. 2017;19:1–26.

    CAS  PubMed  Google Scholar 

  10. Gandhi NS, Mancera RL. The structure of glycosaminoglycans and their interactions with proteins. Chem Biol Drug Des. 2008;72:455–82.

    CAS  PubMed  Google Scholar 

  11. Kuschert GSV, Coulin F, Power CA, Proudfoot AEI, Hubbard RE, Hoogewerf AJ, et al. Glycosaminoglycans interact selectively with chemokines and modulate receptor binding and cellular responses. Biochemistry. 1999;38:12959–68.

    CAS  PubMed  Google Scholar 

  12. Rusnati M, Coltrini D, Oreste P, Zoppetti G, Albini A, Noonan D, et al. Interaction of HIV-1 tat protein with heparin: role of the backbone structure, sulfation, and size. J Biol Chem. 1997;272:11313–20.

    CAS  PubMed  Google Scholar 

  13. de Paz JL, Seeberger PH. Deciphering the glycosaminoglycan code with the help of microarrays. Mol BioSyst. 2008;4:707–11.

    PubMed  Google Scholar 

  14. Gama CI, Hsieh-Wilson LC. Chemical approaches to deciphering the glycosaminoglycan code. Curr Opin Chem Biol. 2005;9:609–19.

    CAS  PubMed  Google Scholar 

  15. Gama CI, Tully SE, Sotogaku N, Clark PM, Rawat M, Vaidehi N, et al. Sulfation patterns of glycosaminoglycans encode molecular recognition and activity. Nat Chem Biol. 2006;2:467–73.

    CAS  PubMed  Google Scholar 

  16. Faham S, Hileman RE, Fromm JR, Linhardt RJ, Rees DC. Heparin structure and interactions with basic fibroblast growth factor. Science. 1996;271:1116–20.

    CAS  PubMed  Google Scholar 

  17. Gallagher JT. Heparan sulfate: growth control with a restricted sequence menu. J Clin Invest. 2001;108:357–61.

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Khan S, Gor J, Mulloy B, Perkins SJ. Semi-rigid solution structures of heparin by constrained X-ray scattering modelling: new insight into heparin-protein complexes. J Mol Biol. 2010;395:504–21.

    CAS  PubMed  Google Scholar 

  19. Khan S, Rodriguez E, Patel R, Gor J, Mulloy B, Perkins SJ. The solution structure of heparan sulphate differs from that of heparin: implications for function. J Biol Chem. 2013;288:27737–51.

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Li W, Johnson DJD, Esmon CT, Huntington JA. Structure of the antithrombin-thrombin-heparin ternary complex reveals the antithrombotic mechanism of heparin. Nat Struct Mol Biol. 2004;11:857–62.

    CAS  PubMed  Google Scholar 

  21. Lubineau A, Lortat-Jacob H, Gavard O, Sarrazin S, Bonnaffe D. Synthesis of tailor-made glycoconjugate mimetics of heparan sulfate that bind IFN-gamma in the nanomolar range. Chem.-Eur. J. 2004;10:4265–82.

    CAS  Google Scholar 

  22. Venkataraman G, Raman R, Sasisekharan V, Sasisekharan R. Molecular characteristics of fibroblast growth factor-fibroblast growth factor receptor-heparin-like glycosaminoglycan complex. Proc Natl Acad Sci U S A. 1999;96:3658–63.

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Karamanos NK, Tzanakakis GN. Glycosaminoglycans: from “cellular glue” to novel therapeutical agents. Curr Opin Pharmacol. 2012;12:220–2.

    CAS  PubMed  Google Scholar 

  24. Volpi N. Therapeutic applications of glycosaminoglycans. Curr Med Chem. 2006;13:1799–810.

    CAS  PubMed  Google Scholar 

  25. Esko JD, Selleck SB. Order out of chaos: assembly of ligand binding sites in heparan sulfate. Annu Rev Biochem. 2002;71:435–71.

    CAS  PubMed  Google Scholar 

  26. Zaia J. On-line separations combined with MS for analysis of glycosaminoglycans. Mass Spectrom Rev. 2009;28:254–72.

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Zaia J. Glycosaminoglycan glycomics using mass spectrometry. Mol Cell Proteomics. 2013;12:885–92.

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Fermas S, Gonnet F, Sutton A, Charnaux N, Mulloy B, Du Y, et al. Sulfated oligosaccharides (heparin and fucoidan) binding and dimerization of stromal cell-derived factor-1 (SDF-1/CXCL 12) are coupled as evidenced by affinity CE-MS analysis. Glycobiology. 2008;18:1054–64.

    CAS  PubMed  Google Scholar 

  29. Fermas S, Gonnet F, Varenne A, Gareil P, Daniel R. Frontal analysis capillary electrophoresis hyphenated to electrospray ionization mass spectrometry for the characterization of the antithrombin/heparin pentasaccharide complex. Anal Chem. 2007;79:4987–93.

    CAS  PubMed  Google Scholar 

  30. Fukui S, Feizi T, Galustian C,  Lawson AM, Chai W. Oligosaccharide microarrays for high-throughput detection and specificity assignments of carbohydrate-protein interactions. Nat Biotechnol. 2002;20:1011–7.

    CAS  PubMed  Google Scholar 

  31. Gray CJ, Sánchez-Ruíz A, Šardzíková I, Ahmed YA, Miller RL, Reyes Martinez JE, et al. Label-free discovery array platform for the characterization of glycan binding proteins and glycoproteins. Anal Chem. 2017;89:4444–51.

    CAS  PubMed  Google Scholar 

  32. Wang D, Liu S,  Trummer BJ, Deng C, Wang A. Carbohydrate microarrays for the recognition of cross-reactive molecular markers of microbes and host cells. Nat Biotechnol. 2002;20:275–81.

    CAS  PubMed  Google Scholar 

  33. Homola J. Surface plasmon resonance sensors for detection of chemical and biological species. Chem Rev. 2008;108:462–93.

    CAS  PubMed  Google Scholar 

  34. Nelson RW, Krone JR, Jansson O. Surface plasmon resonance biomolecular interaction analysis mass spectrometry. 1. Chip-Based Analysis. Anal Chem. 1997;69:4363–8.

    CAS  PubMed  Google Scholar 

  35. Nelson RW, Nedelkov D, Tubbs KA. Biomolecular interaction analysis mass spectometry. BIA/MS can detect and characterize protiens in complex biological fluids at the low- to subfemtomole level. Anal Chem. 2000;72:404A–11A.

    CAS  PubMed  Google Scholar 

  36. Bellon S, Buchmann W, Gonnet F, Jarroux N, Anger-Leroy M, Guillonneau F, et al. Hyphenation of surface plasmon resonance imaging to matrix-assisted laser desorption ionization mass spectrometry by on-chip mass spectrometry and tandem mass spectrometry analysis. Anal Chem. 2009;81:7695–02.

    CAS  PubMed  Google Scholar 

  37. Musso J, Buchmann W, Gonnet F, Jarroux N, Bellon S, Frydman C, et al. Biomarkers probed in saliva by surface plasmon resonance imaging coupled to matrix-assisted laser desorption/ionization mass spectrometry in array format. Anal Bioanal Chem. 2014;407:1285–94.

    PubMed  Google Scholar 

  38. Remy-Martin F, El Osta M, Lucchi G, Zeggari R, Leblois T, Bellon S, et al. Surface plasmon resonance imaging in arrays coupled with mass spectrometry (SUPRA–MS): proof of concept of on-chip characterization of a potential breast cancer marker in human plasma. Anal Bioanal Chem. 2012;404:423–32.

    CAS  PubMed  Google Scholar 

  39. Anders U, Schaefer JV, Hibti F-E, Frydman C, Suckau D, Plückthun A, et al. SPRi-MALDI MS: characterization and identification of a kinase from cell lysate by specific interaction with different designed ankyrin repeat proteins. Anal Bioanal Chem. 2017;409:1827–36.

    CAS  PubMed  Google Scholar 

  40. Sarrazin S, Bonnaffe D, Lubineau A, Lortat-Jacob H. Heparan sulfate mimicry: a synthetic glycoconjugate that recognizes the heparin binding domain of interferon-gamma inhibits the cytokine activity. J Biol Chem. 2005;280:37558–64.

    CAS  PubMed  Google Scholar 

  41. Zhao H, Brown Patrick H, Schuck P. On the distribution of protein refractive index increments. Biophys J. 2011;100:2309–17.

    CAS  PubMed  PubMed Central  Google Scholar 

  42. Tumolo T, Angnes L, Baptista MS. Determination of the refractive index increment (dn/dc) of molecule and macromolecule solutions by surface plasmon resonance. Anal Biochem. 2004;333:273–9.

    CAS  PubMed  Google Scholar 

  43. Przybylski C, Gonnet F, Bonnaffe D, Hersant Y, Lortat-Jacob H, Daniel R. HABA-based ionic liquid matrices for UV-MALDI-MS analysis of heparin and heparan sulfate oligosaccharides. Glycobiology. 2010;20:224–34.

    CAS  PubMed  Google Scholar 

  44. Ropartz D, E BP, Przybylski C, Gonnet F, Daniel R, Fer M, et al. Performance evaluation on a wide set of matrix-assisted laser desorption ionization matrices for the detection of oligosaccharides in a high-throughput mass spectrometric screening of carbohydrate depolymerizing enzymes. Rapid Commun Mass Spectrom. 2011;25:2059–70.

    CAS  PubMed  Google Scholar 

  45. Seffouh A, Milz F, Przybylski C, Laguri C, Oosterhof A, Bourcier S, et al. HSulf sulfatases catalyze processive and oriented 6-O-desulfation of heparan sulfate that differentially regulates fibroblast growth factor activity. FASEB J. 2013;27:2431–9.

    CAS  PubMed  Google Scholar 

  46. Przybylski C, Mokaddem M, Prull-Janssen M, Saesen E, Lortat-Jacob H, Gonnet F, et al. On-line capillary isoelectric focusing hyphenated to native electrospray ionization mass spectrometry for the characterization of interferon-[gamma] and variants. Analyst. 2015;140:543–50.

    CAS  PubMed  Google Scholar 

  47. Lortat-Jacob H, Kleinman HK, Grimaud JA. High-affinity binding of interferon-gamma to a basement membrane complex (matrigel). J Clin Invest. 1991;87:878–83.

    CAS  PubMed  PubMed Central  Google Scholar 

  48. Friand V, Haddad O, Papy-Garcia D, Hlawaty H, Vassy R, Hamma-Kourbali Y, et al. Glycosaminoglycan mimetics inhibit SDF-1/CXCL12-mediated migration and invasion of human hepatoma cells. Glycobiology. 2009;19:1511–24.

    CAS  PubMed  Google Scholar 

  49. Ziarek JJ, Veldkamp CT, Zhang F, Murray NJ, Kartz GA, Liang X, et al. Heparin oligosaccharides inhibit chemokine (CXC motif) ligand 12 (CXCL12) cardioprotection by binding orthogonal to the dimerization interface, promoting oligomerization, and competing with the chemokine (CXC motif) receptor 4 (CXCR4) N terminus. J Biol Chem. 2013;288:737–46.

    CAS  PubMed  Google Scholar 

  50. Sadir R, Baleux F, Grosdidier A, Imberty A, Lortat-Jacob H. Characterization of the stromal cell-derived factor-1-heparin complex. J Biol Chem. 2001;276:8288–96.

    CAS  PubMed  Google Scholar 

  51. Xiao Z, Zhao W, Yang B, Zhang Z, Guan H, Linhardt RJ. Heparinase 1 selectivity for the 3,6-di-O-sulfo-2-deoxy-2-sulfamido-α-D-glucopyranose (1,4) 2-O-sulfo-α-L-idopyranosyluronic acid (GlcNS3S6S-IdoA2S) linkages. Glycobiology. 2011;21:13–22.

    CAS  PubMed  Google Scholar 

  52. Guerrini M, Guglieri S, Casu B, Torri G, Mourier P, Boudier C, et al. Antithrombin-binding octasaccharides and role of extensions of the active pentasaccharide sequence in the specificity and strength of interaction. Evidence for very high affinity induced by an unusual glucuronic acid residue. J Biol Chem. 2008;283:26662–75.

    CAS  PubMed  PubMed Central  Google Scholar 

  53. Schenauer MR, Leary JA. An ion mobility-mass spectrometry investigation of monocyte chemoattractant protein-1. Int J Mass Spectrom. 2009;287:70–6.

    CAS  PubMed  PubMed Central  Google Scholar 

  54. Crown SE, Yu Y, Sweeney MD, Leary JA, Handel TM. Heterodimerization of CCR2 chemokines and regulation by glycosaminoglycan binding. J Biol Chem. 2006;281:25438–46.

    CAS  PubMed  Google Scholar 

  55. Lortat-Jacob H, Baltzer F, Grimaud J-A. Heparin decreases the blood clearance of interferon-γ and increases its activity by limiting the processing of its carboxyl-terminal sequence. J Biol Chem. 1996;271:16139–43.

    CAS  PubMed  Google Scholar 

  56. Lortat-Jacob H, Brisson C, Guerret S, Morel G. Non-receptor-mediated tissue localization of human interferon-γ: role of heparan sulfate/heparin like moelcules. Cytokines. 1996;8:557–66.

    CAS  Google Scholar 

  57. Sadir R, Forest E, Lortat-Jacob H. The heparan sulfate binding sequence of interferon-gamma increased the on rate of the interferon-gamma-interferon-gamma receptor complex formation. J Biol Chem. 1998;273:10919–25.

    CAS  PubMed  Google Scholar 

  58. Camejo EH, Rosengren B, Camejo G, Sartipy P, Fager G, Bondjers G. Interferon gamma binds to extracellular matrix chondroitin-sulfate proteoglycans, thus enhancing its cellular response. Arterioscler Thromb Vasc Biol. 1995;15:1456–65.

    CAS  PubMed  Google Scholar 

  59. Lortat-Jacob H, Grimaud JA. Binding of interferon-gamma to heparan sulfate is restricted to the heparin-like domains and involves carboxylic--but not N-sulfated--groups. Biochim Biophys Acta, Gen Subj. 1992;1117:126–30.

    CAS  Google Scholar 

  60. Lortat-Jacob H, Grimaud JA. Interferon-gamma C-terminal function: new working hypothesis. Heparan sulfate and heparin, new targets for IFN-gamma, protect, relax the cytokine and regulate its activity. Cell Mol Biol. 1991;37:253–60.

    CAS  PubMed  Google Scholar 

  61. Vanhaverbeke C, Simorre JP, Sadir R, Gans P, Lortat-Jacob H. NMR characterization of the interaction between the C-terminal domain of interferon-gamma and heparin-derived oligosaccharides. Biochem J. 2004;384:93–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  62. Lortat-Jacob H, Grimaud J-A. Interferon-γ binds to heparan sulfate by a cluster of amino acids located in the C-terminal part of the molecule. FEBS Lett. 1991;280:152–4.

    CAS  PubMed  Google Scholar 

  63. Hoogewerf AJ, Kuschert GSV, Proudfoot AEI, Borlat F, Clark-Lewis I, Power CA, et al. Glycosaminoglycans mediate cell surface oligomerization of chemokines. Biochemistry. 1997;36:13570–8.

    CAS  PubMed  Google Scholar 

  64. Chakravarty L, Rogers L, Quach T, Breckenridge S, Kolattukudy PE. Lysine 58 and histidine 66 at the C-terminal alpha-helix of monocyte chemoattractant protein-1 are essential for glycosaminoglycan binding. J Biol Chem. 1998;273:29641–7.

    CAS  PubMed  Google Scholar 

  65. Przybylski C, Gonnet F, Hersant Y, Bonnaffe D, Lortat-Jacob H, Daniel R. Desorption electrospray ionization mass spectrometry of glycosaminoglycans and their protein noncovalent complex. Anal Chem. 2010;82:9225–33.

    CAS  PubMed  Google Scholar 

  66. Przybylski C, Gonnet F, Buchmann W, Daniel R. Critical parameters for the analysis of anionic oligosaccharides by desorption electrospray ionization mass spectrometry. J Mass Spectrom. 2012;47:1047–58.

    CAS  PubMed  Google Scholar 

Download references

Author information

Author notes

  1. Cédric Przybylski

    Present address: Institut Parisien de Chimie Moléculaire, IPCM, Sorbonne Université, CNRS, 4 Place Jussieu, 75252, Paris Cedex 05, France

Authors and Affiliations

  1. Laboratoire Analyse et Modélisation pour la Biologie et l’Environnement, LAMBE, Université Paris-Saclay, CNRS, CEA, Univ Evry, Evry, France

    Cédric Przybylski, Florence Gonnet & Régis Daniel

  2. Institut de Biologie Structurale, Université Grenoble Alpes, CNRS, CEA, 38000, Grenoble, France

    Els Saesen & Hugues Lortat-Jacob

Authors
  1. Cédric Przybylski
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Florence Gonnet
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Els Saesen
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hugues Lortat-Jacob
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Régis Daniel
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Cédric Przybylski or Régis Daniel.

Ethics declarations

Conflict of interest

The authors declare that there are no conflicts of interest.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

ESM 1

(PDF 239 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Przybylski, C., Gonnet, F., Saesen, E. et al. Surface plasmon resonance imaging coupled to on-chip mass spectrometry: a new tool to probe protein-GAG interactions. Anal Bioanal Chem 412, 507–519 (2020). https://doi.org/10.1007/s00216-019-02267-2

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00216-019-02267-2

Keywords

Search

Navigation