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Cited by 522Extracellular vesicles in diseaseNanoparticle-Based Drug DeliveryLipid Membrane Structure and Behavior

Formation of a protein corona on the surface of extracellular vesicles in blood plasma

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Tóth, Eszter Á., Turiák, Lilla, Visnovitz, Tamás, Cserép, Csaba, Mázló, Anett, Sódar, Barbara W., Försönits, András I., Petővári, Gábor +10 more·2021·Journal of Extracellular Vesicles
DOI 10.1002/jev2.12140PMC PMC8439280
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Abstract

In this study we tested whether a protein corona is formed around extracellular vesicles (EVs) in blood plasma. We isolated medium‐sized nascent EVs of THP1 cells as well as of Optiprep‐purified platelets, and incubated them in EV‐depleted blood plasma from healthy subjects and from patients with rheumatoid arthritis. EVs were subjected to differential centrifugation, size exclusion chromatography, or density gradient ultracentrifugation followed by mass spectrometry. Plasma protein‐coated EVs had a higher density compared to the nascent ones and carried numerous newly associated proteins. Interactions between plasma proteins and EVs were confirmed by confocal microscopy, capillary Western immunoassay, immune electron microscopy and flow cytometry. We identified nine shared EV corona proteins (ApoA1, ApoB, ApoC3, ApoE, complement factors 3 and 4B, fibrinogen α‐chain, immunoglobulin heavy constant γ2 and γ4 chains), which appear to be common corona proteins among EVs, viruses and artificial nanoparticles in blood plasma. An unexpected finding of this study was the high overlap of the composition of the protein corona with blood plasma protein aggregates. This is explained by our finding that besides a diffuse, patchy protein corona, large protein aggregates also associate with the surface of EVs. However, while EVs with an external plasma protein cargo induced an increased expression of TNF‐α, IL‐6, CD83, CD86 and HLA‐DR of human monocyte‐derived dendritic cells, EV‐free protein aggregates had no effect. In conclusion, our data may shed new light on the origin of the commonly reported plasma protein ‘contamination’ of EV preparations and may add a new perspective to EV research.

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Cited by

Sorted by citations

Authors
Tóth, E. Á., Turiák, L., Visnovitz, T., Cserép, C., Mázló, A., Sódar, B. W., Försönits, A. I., Petővári, G., Sebestyén, A., Komlósi, Z., Drahos, L., Kittel, Á., Nagy, G., Bácsi, A., Dénes, Á., Gho, Y. S., Szabó‐Taylor, K. É., & Buzás, E. I.
Affiliations
  • Semmelweis University (HU)
  • Hungarian Research Network (HU)
  • HUN-REN Institute of Experimental Medicine (HU)
  • University of Debrecen (HU)
  • Pohang University of Science and Technology (KR)
  • Department of Genetics Cell‐ and Immunobiology Semmelweis University Budapest Hungary
Corresponding author
Buzás, Edit I.
ORCID
Venue
Journal of Extracellular Vesicles
Publisher
Wiley
Published
2021-09
Volume
10
Issue
11
Pages
e12140-e12140
ISSN
2001-3078 (ISSN-L)
DOI
10.1002/jev2.12140
PMC
PMC8439280
OpenAlex
W3199740606
Cited by
522
References
7
Citations by year
2026: 128 · 2025: 116 · 2024: 124 · 2023: 80 · 2022: 67 · 2021: 7
FWCI
21.90
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Extracellular Vesicles (publishedVersion, cc-by-nc-nd)
  • Europe PMC (PubMed Central) (publishedVersion, other-oa)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • Repository of the Academy's Library (Library of the Hungarian Academy of Sciences) (acceptedVersion)
  • University of Debrecen Electronic Archive (University of Debrecen) (submittedVersion, other-oa)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Open Access System for Information Sharing (Pohang University of Science and Technology) (submittedVersion)
Funders
  • European Commission (H2020‐MSCA‐ITN‐2017‐722148 TRAIN EV)
  • European Research Council (ERC‐CoG 724994, H2020‐ITN‐2018‐813294‐ENTRAIN)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
  • Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Lipid Membrane Structure and Behavior
Keywords
extracellular vesicles, protein corona, blood plasma, rheumatoid arthritis, platelets, THP-1 cells, apolipoproteins, complement proteins, fibrinogen, immunoglobulins, dendritic cells, TNF-α, interleukin-6, nanoparticle-protein interactions
MeSH terms
Protein Corona, Extracellular Vesicles, Female, Humans, Male, Plasma, Mass Spectrometry

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