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Cited by 56Extracellular vesicles in diseaseNanoparticle-Based Drug DeliveryMicrofluidic and Bio-sensing Technologies

Physical association of low density lipoprotein particles and extracellular vesicles unveiled by single particle analysis

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Lozano‐Andrés, Estefanía, Enciso‐Martinez, Agustin, Gijsbers, Abril, Ridolfi, Andrea, Van Niel, Guillaume, Libregts, Sten F. W. M., Pinheiro, Cláudio, van Herwijnen, Martijn J. C. +7 more·2023·Journal of Extracellular Vesicles
DOI 10.1002/jev2.12376PMC PMC10634195

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Abstract

Extracellular vesicles (EVs) in blood plasma are recognized as potential biomarkers for disease. Although blood plasma is easily obtainable, analysis of EVs at the single particle level is still challenging due to the biological complexity of this body fluid. Besides EVs, plasma contains different types of lipoproteins particles (LPPs), that outnumber EVs by orders of magnitude and which partially overlap in biophysical properties such as size, density and molecular makeup. Consequently, during EV isolation LPPs are often co‐isolated. Furthermore, physical EV‐LPP complexes have been observed in purified EV preparations. Since co‐isolation or association of LPPs can impact EV‐based analysis and biomarker profiling, we investigated the presence and formation of EV‐LPP complexes in biological samples by using label‐free atomic force microscopy, cryo‐electron tomography and synchronous Rayleigh and Raman scattering analysis of optically trapped particles and fluorescence‐based high sensitivity single particle flow cytometry. Furthermore, we evaluated the impact on flow cytometric analysis in the presence of LPPs using in vitro spike‐in experiments of purified tumour cell line‐derived EVs in different classes of purified human LPPs. Based on orthogonal single‐particle analysis techniques we demonstrate that EV‐LPP complexes can form under physiological conditions. Furthermore, we show that in fluorescence‐based flow cytometric EV analysis staining of LPPs, as well as EV‐LPP associations, can influence quantitative and qualitative EV analysis. Lastly, we demonstrate that the colloidal matrix of the biofluid in which EVs reside impacts their buoyant density, size and/or refractive index (RI), which may have consequences for down‐stream EV analysis and EV biomarker profiling.

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Authors
Lozano‐Andrés, E., Enciso‐Martinez, A., Gijsbers, A., Ridolfi, A., Van Niel, G., Libregts, S. F. W. M., Pinheiro, C., van Herwijnen, M. J. C., Hendrix, A., Brucale, M., Valle, F., Peters, P. J., Otto, C., Arkesteijn, G. J. A., & Wauben, M. H. M.
Affiliations
  • Department of Biomolecular Health Sciences, Faculty of Veterinary Medicine Utrecht University Utrecht The Netherlands
  • Leiden University Medical Center (NL)
  • Maastricht University (NL)
  • Vrije Universiteit Amsterdam (NL)
  • Institute for Psychiatry and Neuroscience of Paris Hopital Saint‐Anne, Université Descartes Paris France
  • Utrecht University (NL)
  • Ghent University (BE)
  • Institute of Nanostructured Materials (IT)
  • University of Twente (NL)
Corresponding author
Wauben, Marca H. M.
ORCID
Venue
Journal of Extracellular Vesicles
Publisher
Wiley
Published
2023-11
Volume
12
Issue
11
Pages
e12376-e12376
ISSN
2001-3078 (ISSN-L)
DOI
10.1002/jev2.12376
PMC
PMC10634195
OpenAlex
W4388528065
Cited by
56
References
1
Citations by year
2026: 15 · 2025: 21 · 2024: 16 · 2023: 4
FWCI
4.97
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Extracellular Vesicles (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Research Publications (Maastricht University) (publishedVersion, cc-by)
  • VU Research Portal (publishedVersion, other-oa)
  • University of Twente Research Information (publishedVersion, cc-by)
  • Leiden Repository (Leiden University) (submittedVersion, cc-by)
  • Ghent University Academic Bibliography (Ghent University) (submittedVersion, cc-by)
  • HAL (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Utrecht University Repository (Utrecht University) (submittedVersion, other-oa)
  • University of Twente Research Information (submittedVersion)
Funders
Fondation pour la Recherche Médicale (AJE20160635884)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
  • Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
  • Physical Sciences › Engineering › Biomedical Engineering › Microfluidic and Bio-sensing Technologies
Keywords
extracellular vesicles, low-density lipoprotein, lipoprotein particles, plasma, buoyant density, refractive index, flow cytometry, single-particle analysis, cryo-electron tomography, atomic force microscopy, biomarker profiling
MeSH terms
Extracellular Vesicles, Single Molecule Imaging, Humans, Lipoproteins, LDL, Biomarkers, Cell Line, Tumor

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