A pioneering study from Kanazawa University’s Nano Life Science Institute (WPI-NanoLSI) has unveiled a novel application of high-speed atomic force microscopy (HS-AFM) videography to visualise small extracellular vesicles (sEVs) in unprecedented detail.

These nanoscale particles, crucial for intercellular communication, have been challenging to study due to their minute size and dynamic nature. 

Led by researchers Keesiang Lim and Richard W. Wong, the team employed HS-AFM to capture real-time, nanometer-resolution images of sEVs derived from HEK293T cells. This technique allowed them to observe the vesicles’ surface structures and interactions under near-physiological conditions without the need for extensive sample preparation. 

The study revealed two distinct sEV subpopulations: smaller vesicles (≤100 nm) exhibited greater membrane rigidity and higher concentrations of exosomal markers like CD63 and CD81, suggesting an endosomal origin. In contrast, larger vesicles (>100 nm) showed more structural variability, indicating a different biogenesis pathway. 

“By leveraging HS-AFM videography, we can now directly observe the dynamic interactions of surface markers on individual sEVs, paving the way for the development of high-precision EV-based biomarkers,” said Wong. 

The researchers suggest that the method could contribute to advancements in targeted drug delivery and regenerative medicine by enabling more precise characterisation of therapeutic EVs. 

The full study is available in the Journal of Extracellular Vesicles.