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.