ABSTRACT
Exosomes are membrane nanovesicles that intermediate cell-to-cell signaling through the transfer of their molecular cargo. The exosomes’ small size facilitates rapid migration through the extracellular matrix and into and out of circulation. Here we report that the mobility of the exosomes is much lower than would be expected from the size of their membrane vesicles. The difference is broadly distributed and caused by surface proteins, which significantly impede exosome migration. The observed wide range in the mobility implies that a subpopulation of hydrodynamically small exosomes is more likely to participate in signaling. The extracellular environment amplifies the size-dependent hindrance to the exosomes migration. The significant contribution of surface proteins to the transport resistance make the exosome mobility a dynamic property that changes with the extracellular environment which affects the membrane protein conformation, glycosylation, specific, and non-specific surface adsorption.
ABBREVIATIONS
- Aβ
- gliotoxic amyloid-β peptides
- AFM
- Atomic-force microscopy
- ALIX
- programmed cell death 6 interacting protein
- ANXA5
- Annexin A5 protein
- CD63 and CD81
- tetraspanin proteins encoded by the CD63 and CD81 genes respectively
- DLS
- dynamic light scattering
- ECM
- extracellular matrix
- ECS
- extracellular space
- EpCAM
- epithelial cell adhesion glycoprotein
- ER+
- estrogen-receptor-positive
- EV
- extracellular vesicles
- FLOT1
- Flotillin-1 protein
- GM130
- cis-Golgi matrix protein
- ICAM
- Intercellular Adhesion Molecule 1
- MCF7
- Michigan Cancer Foundation-7 breast cancer cell line
- miR-21
- a microRNA encoded by MIR21 gene
- microRNA
- short non-coding RNA molecule
- MSD
- mean squared displacements
- NP
- nanoparticle
- NTA
- nanoparticle tracking analysis
- PBS
- phosphate-buffered saline
- PCR
- polymerase chain reaction
- probability density function
- PK
- proteinase K
- SEofM
- standard error of the mean
- SI
- Supporting Information
- TEM
- transmission electron microscopy
- TSG101
- tumor susceptibility gene 101 protein.