Single extracellular vesicle imaging and computational analysis identifies inherent architectural heterogeneity

Extracellular vesicles (EVs) have emerged as key players in intercellular communication, carrying molecular cargo that influences various physiological and pathological processes in the body. Understanding the heterogeneity of EVs is crucial for unraveling their complex actions and biodistribution, which can have significant implications for both basic research and clinical applications.

In a recent study, researchers at The University of Texas MD Anderson Cancer Center utilized cryogenic transmission electron microscopy (cryo-TEM) to investigate the architectural heterogeneity of EVs. Cryo-TEM is a powerful imaging technique that allows researchers to visualize biological samples at high resolution without the need for harsh labeling methods, thereby preserving their native conformation.

The study examined EVs isolated from different sources, including cancer cells, normal cells, immortalized cells, and various body fluids. By imaging thousands of individual EVs and utilizing a segmentation neural network model, the researchers identified a structural atlas of EV shapes.

The results revealed that EVs exhibit consistent architectural heterogeneity across different sources, regardless of the purification techniques used. The majority of EVs observed were single spherical structures, but rod-like or tubular shapes, as well as double structures, were also identified.

Quantitative analysis of the EVs showed an average eccentricity of 0.5366 ± 0.2 and an average equivalent diameter of 132.43 ± 67 nm. These findings provide valuable insights into the structural diversity of EVs and lay the groundwork for future studies exploring their biological impact.

By establishing a reference foundation for high-resolution images of EVs, this study paves the way for further research into their roles in intercellular communication, disease pathogenesis, and potential therapeutic applications. Understanding the intricate architecture of EVs will contribute to our knowledge of their function and enable the development of novel strategies for diagnosing and treating a wide range of diseases.

Kapoor KS, Kong S, Sugimoto H, Guo W, Boominathan V, Chen YL, Biswal SL, Terlier T, McAndrews KM, Kalluri R. (2024) Single Extracellular Vesicle Imaging and Computational Analysis Identifies Inherent Architectural Heterogeneity. ACS Nano [Epub ahead of print]. [abstract]

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