Skip to main content
SpringerLink
Log in

C1q recognizes antigen-bound IgG in a curvature-dependent manner

  • Research Article
  • Published:
Nano Research Aims and scope Submit manuscript

Abstract

C1q is an important recognition protein in the complement system, which is a major protein cascade in the innate immune system. Upon recognition of a target by C1q, the target is marked for opsonization and destruction. C1q recognizes many pathogenic patterns directly, but an important target is the Fc domain of antibodies binding to their antigen. In this paper, the curvature-dependence of the interaction between IgG and C1q is studied by surface plasmon resonance and quartz crystal microbalance. IgG is organized in similar surface coverage densities on flat polystyrene surfaces and polystyrene nanoparticles of different sizes, and the amount of C1q binding to the IgG is investigated. Nanoparticles in solution were found to aggregate upon incubation with IgG, and therefore a new technique utilizing nanoparticles binding to antifouling polymer brush functionalized surfaces was used to prepare surfaces with nanoparticles for measurements with surface plasmon resonance. Interestingly antigen-bound IgG at the curved surface of nanoparticles showed 5.6 times lower binding of C1q compared to at matched flat surfaces. There was no significant difference between the binding at 100 and 200 nm polystyrene particles. These findings are important for designing drug delivery systems to evade the complement system.

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

Similar content being viewed by others

References

  1. Dobrovolskaia, M. A.; McNeil, S. E. Immunological properties of engineered nanomaterials. Nat. Nanotechnol. 2007, 2, 469–478.

    Article  CAS  Google Scholar 

  2. Dobrovolskaia, M. A.; Aggarwal, P.; Hall, J. B.; Mcneil, S. E. Preclinical studies to understand nanoparticle interaction with the immune system and its potential effects on nanoparticle biodistribution. Mol. Pharmaceutics2008, 5, 487–495.

    Article  CAS  Google Scholar 

  3. Moghimi, S. M.; Simberg, D. Complement activation turnover on surfaces of nanoparticles. Nano Today2017, 15, 8–10.

    Article  CAS  Google Scholar 

  4. Ugurlar, D.; Howes, S. C.; de Kreuk, B. J.; Koning, R. I.; De Jong, R. N.; Beurskens, F. J.; Schuurman, J.; Koster, A. J.; Sharp, T. H. et al. Structures of C1-IgG1 provide insights into how danger pattern recognition activates complement. Science2018, 359, 794–797.

    Article  CAS  Google Scholar 

  5. Galvan, M. D.; Greenlee-Wacker, M. C.; Bohlson, S. S. C1q and phagocytosis: The perfect complement to a good meal. J. Leukoc. Biol. 2012, 92, 489–497.

    Article  CAS  Google Scholar 

  6. Schneider, S.; Zacharias, M. Atomic resolution model of the antibody Fc interaction with the complement C1q component. Mol. Immunol. 2012, 51, 66–72.

    Article  CAS  Google Scholar 

  7. NayaK, A.; Pednekar, L.; Reid, K. B.; Kishore, U. Complement and non-complement activating functions of C1q: A prototypical innate immune molecule. Innate Immun. 2012, 18, 350–363.

    Article  CAS  Google Scholar 

  8. Ricklin, D.; Hajishengallis, G.; Yang, K.; Lambris, J. D. Complement: A key system for immune surveillance and homeostasis. Nat. Immunol. 2010, 11, 785–797.

    Article  CAS  Google Scholar 

  9. Sim, R. B.; Wallis, R. Immune attack on nanoparticles. Nat. Nanotechnol. 2011, 6, 80–81.

    Article  CAS  Google Scholar 

  10. Gaboriaud, C.; Juanhuix, J.; Gruez, A.; Lacroix, M.; Darnault, C.; Pignol, D.; Verger, D.; Fontecilla-Camps, J. C.; Arlaud, G. J. The crystal structure of the globular head of complement protein C1q provides a basis for its versatile recognition properties. J. Biol. Chem. 2003, 278, 46974–46982.

    Article  CAS  Google Scholar 

  11. Lee, C. H.; Romain, G.; Yan, W. P.; Watanabe, M.; Charab, W.; Todorova, B.; Lee, J.; Triplett, K.; Donkor, M.; Lungu, O. I. et al. IgG Fc domains that bind C1q but not effector Fcγ receptors delineate the importance of complement-mediated effector functions. Nat. Immunol. 2017, 18, 889–898.

    Article  CAS  Google Scholar 

  12. Diebolder, C. A.; Beurskens, F. J.; de Jong, R. N.; Koning, R. I.; Strumane, K.; Lindorfer, M. A.; Voorhorst, M.; Ugurlar, D.; Rosati, S.; Heck, A. J. R. et al. Complement is activated by IgG hexamers assembled at the cell surface. Science2014, 343, 1260–1263.

    Article  CAS  Google Scholar 

  13. Gaboriaud, C.; Thielens, N. M.; Gregory, L. A.; Rossi, V.; Fontecilla- Camps, J. C.; Arlaud, G. J. Structure and activation of the C1 complex of complement: Unraveling the puzzle. Trends Immunol. 2004, 25, 368–373.

    Article  CAS  Google Scholar 

  14. Gadjeva, M. G.; Rouseva, M. M.; Zlatarova, A. S.; Reid, K. B. M.; Kishore, U.; Kojouharova, M. S. Interaction of human C1q with IgG and IgM: Revisited. Biochemistry2008, 47, 13093–13102.

    Article  CAS  Google Scholar 

  15. Boraschi, D.; Italiani, P.; Palomba, R.; Decuzzi, P.; Duschl, A.; Fadeel, B.; Moghimi, S. M. Nanoparticles and innate immunity: New perspectives on host defence. Semin. Immunol. 2017, 34, 33–51.

    Article  CAS  Google Scholar 

  16. Strasser, J.; de Jong, R. N.; Beurskens, F. J.; Schuurman, J.; Parren, P. W. H. I.; Hinterdorfer, P.; Preiner, J. Weak fragment crystallizable (Fc) domain interactions drive the dynamic assembly of IgG oligomers upon antigen recognition. ACS Nano2020, 14, 2739–2750

    Article  CAS  Google Scholar 

  17. Strasser, J.; de Jong, R. N.; Beurskens, F. J.; Wang, G. B.; Heck, A. J. R.; Schuurman, J.; Parren, P. W. H. I.; Hinterdorfer, P.; Preiner, J. Unraveling the macromolecular pathways of IgG oligomerization and complement activation on antigenic surfaces. Nano Lett. 2019, 19, 4787–4796.

    Article  CAS  Google Scholar 

  18. Lundqvist, M.; Stigler, J.; Elia, G.; Lynch, L.; Cedervall, T.; Dawson, K. A. Nanoparticle size and surface properties determine the protein corona with possible implications for biological impacts. Proc. Natl. Acad. Sci. USA2008, 105, 14265–14270.

    Article  CAS  Google Scholar 

  19. Pedersen, M. B.; Zhou, X. F.; Larsen, E. K. U.; Sørensen, U. S.; Kjems, J.; Nygaard, J. V.; Nyengaard, J. R.; Meyer, R. L.; Boesen, T.; Vorup-Jensen, T. Curvature of synthetic and natural surfaces is an important target feature in classical pathway complement activation. J. Immunol. 2010, 184, 1931–1945.

    Article  CAS  Google Scholar 

  20. Hulander, M.; Lundgren, A.; Berglin, M.; Ohrlander, M.; Lausmaa, J.; Elwing, H. Immune complement activation is attenuated by surface nanotopography. Int. J. Nanomedicine2011, 6, 2653–2666.

    Article  CAS  Google Scholar 

  21. Westas Janco, E.; Hulander, M.; Andersson, M. Curvature-dependent effects of nanotopography on classical immune complement activation. Acta Biomaterialia2018, 74, 112–120.

    Article  CAS  Google Scholar 

  22. Zeuthen, C. M.; Shahrokhtash, A.; Sutherland, D. S. Nanoparticle adsorption on antifouling polymer brushes. Langmuir2019, 35, 14879–14889.

    Article  CAS  Google Scholar 

  23. Vogt, B. D.; Lin, E. K.; Wu, W. I.; White, C. C. Effect of film thickness on the validity of the sauerbrey equation for hydrated polyelectrolyte films. J. Phys. Chem. B2004, 108, 12685–12690.

    Article  CAS  Google Scholar 

  24. Konradi, R.; Textor, M.; Reimhult, E. Using complementary acoustic and optical techniques for quantitative monitoring of biomolecular adsorption at interfaces. Biosensors2012, 2, 341–376.

    Article  CAS  Google Scholar 

  25. Voinova, M. V; Rodahl, M.; Jonson, M.; Kasemo, B. Viscoelastic acoustic response of layered polymer films at fluid-solid interfaces: Continuum mechanics approach. Phys. Scr. 1999, 59, 391–396.

    Article  CAS  Google Scholar 

  26. Ouberai, M. M.; Xu, K. R.; Welland, M. E. Effect of the interplay between protein and surface on the properties of adsorbed protein layers. Biomaterials2014, 35, 6157–6163.

    Article  CAS  Google Scholar 

  27. Reviakine, I.; Johannsmann, D.; Richter, R. P. Hearing what you cannot see and visualizing what you hear: Interpreting quartz crystal microbalance data from solvated interfaces. Anal. Chem. 2011, 83, 8838–8848.

    Article  CAS  Google Scholar 

  28. Reimhult, E.; Larsson, C.; Kasemo, B.; Höök, F. Simultaneous surface plasmon resonance and quartz crystal microbalance with dissipation monitoring measurements of biomolecular adsorption events involving structural transformations and variations in coupled water. Anal. Chem. 2004, 76, 7211–7220.

    Article  CAS  Google Scholar 

  29. Malmström, J.; Agheli, H.; Kingshott, P.; Sutherland, D. S. Viscoelastic modeling of highly hydrated laminin layers at homogeneous and nanostructured surfaces: Quantification of protein layer properties using QCM-D and SPR. Langmuir2007, 23, 9760–9768.

    Article  Google Scholar 

  30. Aisen, P.; Listowsky, I. Iron transport and storage proteins. Annu. Rev. Biochem. 1980, 49, 357–393.

    Article  CAS  Google Scholar 

  31. Adamczyk, Z.; Siwek, B.; Zembala, M.; Belouschek, P. Kinetics of localized adsorption of colloid particles. Adv. Colloid Interface Sci. 1994, 48, 151–280.

    Article  Google Scholar 

  32. Tan, Y. H.; Liu, M. Z.; Nolting, B.; Go, J. G.; Gervay-Hague, J.; Liu, G. Y. A nanoengineering approach for investigation and regulation of protein immobilization. ACS Nano2008, 2, 2374–2384.

    Article  CAS  Google Scholar 

  33. Strang, C. J.; Siegel, R. C.; Phillips, M. L.; Poon, P. H.; Schumaker, V. N. Ultrastructure of the first component of human complement: Electron microscopy of the crosslinked complex. Proc. Natl. Acad. Sci. USA1982, 79, 586–590.

    Article  CAS  Google Scholar 

  34. Mortensen, S. A.; Sander, B.; Jensen, R. K.; Pedersen, J. S.; Golas, M. M.; Jensenius, J. C.; Hansen, A. G.; Thiel, S.; Andersen, G. R. Structure and activation of C1, the complex initiating the classical pathway of the complement cascade. Proc. Natl. Acad. Sci. USA2017, 114, 986–991.

    Article  CAS  Google Scholar 

  35. Larsson, C.; Rodahl, M.; Höök, F. Characterization of DNA Immobilization and subsequent hybridization on a 2D arrangement of streptavidin on a biotin-modified lipid bilayer supported on SiO2. Anal. Chem. 2003, 75, 5080–5087.

    Article  CAS  Google Scholar 

  36. Saptarshi, S. R.; Duschl, A.; Lopata, A. L. Interaction of nanoparticles with proteins: Relation to bio-reactivity of the nanoparticle. J. Nanobiotechnology2013, 11, 26.

    Article  CAS  Google Scholar 

  37. Tenner, A. J.; Lesavre, P. H.; Cooper, N. R. Purification and radiolabeling of human C1q. J. Immunol. 1981, 127, 648–653.

    CAS  Google Scholar 

Download references

Acknowledgements

We kindly acknowledge Folmer Lyckegaard and Jacques Chevallier for sputter-coating the SPR chips and Bo Nilsson for valuable discussions. This work acknowledges funding from the FNU project DFF-4181-00473, the Danish National Research Foundation center grant CellPAT (DNRF135), Sino-Danish Centre for Education and Research and the European Community’s Seventh Framework Programme under grant agreement No. 602699 (DIREKT)

Author information

Authors and Affiliations

  1. Interdisciplinary Nanoscience Center, Aarhus University, Gustav Wieds vej 14, 8000, Aarhus C, Denmark

    Christina M. Zeuthen, Ali Shahrokhtash, Hossein Mohammad-Beigi & Duncan S. Sutherland

  2. Department of Immunology, Genetics and Pathology, Uppsala University, Dag Hammarskjölds väg 20, 751 85, Uppsala, Sweden

    Karin Fromell & Kristina Nilsson Ekdahl

  3. Linnaeus Center of Biomaterials Chemistry, Linnaeus University, 391 82, Kalmar, Sweden

    Kristina Nilsson Ekdahl

  4. Sino-Danish Center for Education and Research, Niels Jensens Vej 2, Building 1190, 8000, Aarhus C, Denmark

    Christina M. Zeuthen

  5. The Centre for Cellular Signal Patterns (CellPAT), Gustav Wieds vej 14, 8000, Aarhus C, Denmark

    Christina M. Zeuthen, Ali Shahrokhtash, Hossein Mohammad-Beigi & Duncan S. Sutherland

Authors
  1. Christina M. Zeuthen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ali Shahrokhtash
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Karin Fromell
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Kristina Nilsson Ekdahl
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hossein Mohammad-Beigi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Duncan S. Sutherland
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Duncan S. Sutherland.

Electronic Supplementary Material

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zeuthen, C.M., Shahrokhtash, A., Fromell, K. et al. C1q recognizes antigen-bound IgG in a curvature-dependent manner. Nano Res. 13, 1651–1658 (2020). https://doi.org/10.1007/s12274-020-2788-7

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12274-020-2788-7

Keywords

Search

Navigation