Identification of distinct nanoparticles and subsets of extracellular vesicles by asymmetric-flow field-flow fractionation

By Haiying Zhang, D. Freitas, Han Sang Kim, K. Fabijanic, Zhong Li, Haiyan Chen, M. T. Mark, H. Molina, A. Martin, L. Bojmar and 32 more. Nature Cell Biology, 2018

1,416 citations recorded by the source corpus.

The heterogeneity of exosomal populations has hindered our understanding of their biogenesis, molecular composition, biodistribution and functions. By employing asymmetric flow field-flow fractionation (AF4), we identified two exosome subpopulations (large exosome vesicles, Exo-L, 90–120 nm; small exosome vesicles, Exo-S, 60–80 nm) and discovered an abundant population of non-membranous nanoparticles termed ‘exomeres’ (~35 nm). Exomere proteomic profiling revealed an enrichment in metabolic enzymes and hypoxia, microtubule and coagulation proteins as well as specific pathways, such as glycolysis and mTOR signalling. Exo-S and Exo-L contained proteins involved in endosomal function and secretion pathways, and mitotic spindle and IL-2/STAT5 signalling pathways, respectively. Exo-S, Exo-L and exomeres each had unique N-glycosylation, protein, lipid, DNA and RNA profiles and biophysical properties. These three nanoparticle subsets demonstrated diverse organ biodistribution patterns, suggesting distinct biological functions. This study demonstrates that AF4 can serve as an improved analytical tool for isolating extracellular vesicles and addressing the complexities of heterogeneous nanoparticle subpopulations. Lyden and colleagues use asymmetric flow field-flow fractionation to classify nanoparticles derived from cell lines and human samples, including previously uncharacterized large, Exo-L and small, Exo-S, exosome subsets.

Subfields: Cancer Research, Computational Mechanics, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/4e4d3ee0d160c91f3b30df90342ffa095f764d58

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In Cancer Research

1. Valerie S. LeBleu
2. M. Wood
3. Lin Zhang
4. Dihua Yu
5. P. Vader
6. Raghu Kalluri
7. D. Hanahan

In Molecular Biology

1. Valerie S. LeBleu
2. P. Vader
3. Raghu Kalluri
4. Imre Mäger
5. M. Wood
6. Lin Zhang
7. Dihua Yu
8. M. Nieto

Citations in the corpus

• The biology, function, and biomedical applications of exosomes (2020, positive): “Refined fractionation methods involving EVs revealed that exosomes may contain subpopulations defined by a distinct size range (17).”
• Exosomes in cancer development, metastasis, and immunity (2019, background): “Recently, Lyden and colleagues identified two exosome subpopulations: large exosome vesicles (Exo-L), sized 90–120 nm, and small exosome vesicles (Exo-S), sized 60–80 nm [5].”
• Extracellular Vesicle Heterogeneity: Subpopulations, Isolation Techniques, and Diverse Functions in Cancer Progression (2018, background): “Two distinct subpopulations of EXOs, Exo-L (large EXO vesicles, 90–120 nm) and Exo-S (small EXO vesicles, 60–80 nm), were isolated and characterized (105).”