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Nano Research 2020, 13(6): 1651-1658 https://doi.org/10.1007/s12274-020-2788-7
Research Article | Issue | Published: 07 May 2020

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

Show Author's Information Christina M. Zeuthen1,4,5,  Ali Shahrokhtash1,5,  Karin Fromell2,  Kristina Nilsson Ekdahl2,3,  Hossein Mohammad-Beigi1,5,  Duncan S. Sutherland1,5( )
Interdisciplinary Nanoscience Center, Aarhus University, Gustav Wieds vej 14, 8000 Aarhus C, Denmark
Department of Immunology, Genetics and Pathology, Uppsala University, Dag Hammarskjölds väg 20, 751 85 Uppsala, Sweden
Linnaeus Center of Biomaterials Chemistry, Linnaeus University, 391 82 Kalmar, Sweden
Sino-Danish Center for Education and Research, Niels Jensens Vej 2, Building 1190, 8000 Aarhus C, Denmark
The Centre for Cellular Signal Patterns (CellPAT), Gustav Wieds vej 14, 8000 Aarhus C, Denmark
Keywords:
nanoparticles, antibodies, C1q, complement system, curvature
Topics:
Antigens NanoparticlesPlasmonsProteinsSurface plasmon resonance
Cite this article:
M. Zeuthen C, Shahrokhtash A, Fromell K, et al. C1q recognizes antigen-bound IgG in a curvature-dependent manner. Nano Research, 2020, 13(6): 1651-1658. https://doi.org/10.1007/s12274-020-2788-7
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Abstract Full text Electronic supplementary material About this article

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.


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Electronic supplementary material
About this article

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

Show Author's information Christina M. Zeuthen1,4,5, Ali Shahrokhtash1,5, Karin Fromell2, Kristina Nilsson Ekdahl2,3, Hossein Mohammad-Beigi1,5, Duncan S. Sutherland1,5( )
Interdisciplinary Nanoscience Center, Aarhus University, Gustav Wieds vej 14, 8000 Aarhus C, Denmark
Department of Immunology, Genetics and Pathology, Uppsala University, Dag Hammarskjölds väg 20, 751 85 Uppsala, Sweden
Linnaeus Center of Biomaterials Chemistry, Linnaeus University, 391 82 Kalmar, Sweden
Sino-Danish Center for Education and Research, Niels Jensens Vej 2, Building 1190, 8000 Aarhus C, Denmark
The Centre for Cellular Signal Patterns (CellPAT), Gustav Wieds vej 14, 8000 Aarhus C, Denmark

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.

Keywords: nanoparticles, antibodies, C1q, complement system, curvature

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Publication history
Copyright
Acknowledgements

Publication history

Received: 25 February 2020
Revised: 01 April 2020
Accepted: 03 April 2020
Published: 07 May 2020
Issue date: June 2020

Copyright

© Tsinghua University Press and Springer-Verlag GmbH Germany, part of Springer Nature 2020

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)

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