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

Abstract:

: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.

journal_name

Nat Cell Biol

journal_title

Nature cell biology

authors

Zhang H,Freitas D,Kim HS,Fabijanic K,Li Z,Chen H,Mark MT,Molina H,Martin AB,Bojmar L,Fang J,Rampersaud S,Hoshino A,Matei I,Kenific CM,Nakajima M,Mutvei AP,Sansone P,Buehring W,Wang H,Jimenez JP,Cohen-Gould L,P

doi

10.1038/s41556-018-0040-4

subject

Has Abstract

pub_date

2018-03-01 00:00:00

pages

332-343

issue

3

eissn

1465-7392

issn

1476-4679

pii

10.1038/s41556-018-0040-4

journal_volume

20

pub_type

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