Non-contact microfluidic analysis of the stiffness of single large extracellular vesicles from IDH1-mutated glioblastoma cells

Abstract

In preparation for leveraging extracellular vesicles (EVs) for disease diagnostics and therapeutics, fundamental research is being done to understand EV biological, chemical, and physical properties. Most published studies investigate nanoscale EVs and focus on EV biochemical content. There is much less understanding of large microscale EV characteristics and EV mechanical properties. We recently introduced a non-contact microfluidic technique that measures the stiffness of large EVs (>1 μm diameter). This study probes the sensitivity of the microfluidic technique to distinguish between EV populations by comparing stiffness distributions of large EVs derived from glioblastoma cell lines. EVs derived from cells expressing the IDH1 mutation, a common glioblastoma mutation known to disrupt lipid metabolism, were significantly stiffer than those expressed from wild-type cells. A supporting lipidomics analysis shows that the IDH1 mutation increases the amount of saturated lipids in EVs. Taken together, these data suggest that high-throughput microfluidics is capable of distinguishing between large EV populations that differ in biomolecular composition and therefore structure. These findings advance the understanding of EV biomechanics, in particular for the less studied microscale EVs, and demonstrate microfluidics to be a promising technique to perform clinical EV mechanophenotyping.