Kanazawa University research: Decoding how cells communicate by high-speed imaging of molecular couriers

KANAZAWA, Japan, April 3, 2025 /PRNewswire/ -- Nano Life Science Institute (WPI-NanoLSI), Kanazawa University, demonstrates a novel approach for nanoscopic profiling of small extracellular vesicles (sEVs) using high-speed atomic force microscopy (HS-AFM) videography. This pioneering method provides an unprecedented level of detail in characterizing sEV subpopulations, offering new insights into their biological roles and potential applications in disease diagnostics.

Extracellular vesicles (EVs), including exosomes and microvesicles, play a crucial role in intercellular communication by transferring biomolecules such as proteins, lipids, and RNA. These tiny vesicles act as molecular couriers, shuttling messages between cells to regulate immune responses, tissue repair, and even disease progression. Despite their significance, the accurate characterization of these nanoscale vesicles remains a major challenge due to their small size and heterogeneity. Existing techniques, such as nanoparticle tracking analysis (NTA) and flow cytometry, lack the resolution to provide precise structural and compositional information at the single-vesicle level.

In this study, led by Keesiang Lim and Richard W. Wong, the team utilized HS-AFM to visualize the nanotopology of sEVs derived from HEK293T cells under physiological conditions. Their findings revealed distinct sEV subpopulations enriched with specific exosome markers, such as CD63 and CD81. Notably, they observed that sEVs smaller than 100 nm exhibited greater membrane rigidity and higher co-localization with exosomal markers compared to larger vesicles, which showed significant height fluctuations.

"Our study represents a major advancement in extracellular vesicle research," says Wong. "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."

This nanoscopic immunophenotyping approach has the potential to revolutionize early disease detection, particularly in cancer diagnostics, where exosome-based biomarkers are gaining attention. Additionally, the method could contribute to advancements in targeted drug delivery and regenerative medicine by enabling more precise characterization of therapeutic EVs.

Glossary

• Molecular Couriers: Small extracellular vesicles (sEVs) that transport biomolecules between cells, facilitating intercellular communication.
• High-Speed Atomic Force Microscopy (HS-AFM): A high-resolution imaging technique that enables real-time visualization of nanoscale structures and dynamic biological processes.
• Nanotopology: The study of surface structures and nanoscale features of biological entities, such as extracellular vesicles, under physiological conditions.
• Immunophenotyping: The process of identifying specific biomolecular markers on cell-derived vesicles using antibodies to differentiate subpopulations.

Reference

Muhammad Isman Sandira, Keesiang Lim, Takeshi Yoshida, Elma Sakinatus Sajidah, Shinnosuke Narimatsu, Reon Imakawa, Kota Yoshimura, Goro Nishide, Yujia Qiu, Azuma Taoka, Masaharu Hazawa, Toshio Ando, Rikinari Hanayama, Richard W Wong, Nanoscopic Profiling of Small Extracellular Vesicles via High-Speed Atomic Force Microscopy (HS-AFM) Videography, Journal of Extracellular Vesicles March 2025

DOI: 10.1002/jev2.70050

URL: https://isevjournals.onlinelibrary.wiley.com/doi/full/10.1002/jev2.70050

Funding

The research was supported by the World Premier International Research Center Initiative (WPI) of MEXT, Japan, along with funding from JST SPRING, MEXT/JSPS KAKENHI, JST CREST, Hokuriku Bank, Takeda Science Foundation, and Shimadzu Science Foundation.

Contact
Kimie Nishimura (Ms)
Project Planning and Outreach, NanoLSI Administration Office
Nano Life Science Institute, Kanazawa University
Email: nanolsi-office@adm.kanazawa-u.ac.jp
Kakuma-machi, Kanazawa 920-1192, Japan

About Nano Life Science Institute (WPI-NanoLSI), Kanazawa University

Understanding nanoscale mechanisms of life phenomena by exploring "uncharted nano-realms".

Cells are the basic units of almost all life forms. We are developing nanoprobe technologies that allow direct imaging, analysis, and manipulation of the behavior and dynamics of important macromolecules in living organisms, such as proteins and nucleic acids, at the surface and interior of cells. We aim at acquiring a fundamental understanding of the various life phenomena at the nanoscale.

https://nanolsi.kanazawa-u.ac.jp/en/

About the World Premier International Research Center Initiative (WPI)

The WPI program was launched in 2007 by Japan's Ministry of Education, Culture, Sports, Science and Technology (MEXT) to foster globally visible research centers boasting the highest standards and outstanding research environments. Numbering more than a dozen and operating at institutions throughout the country, these centers are given a high degree of autonomy, allowing them to engage in innovative modes of management and research. The program is administered by the Japan Society for the Promotion of Science (JSPS).

See the latest research news from the centers at the WPI News Portal:

https://www.eurekalert.org/newsportal/WPI
Main WPI program site: www.jsps.go.jp/english/e-toplevel 

About Kanazawa University

As the leading comprehensive university on the Sea of Japan coast, Kanazawa University has contributed greatly to higher education and academic research in Japan since it was founded in 1949. The University has three colleges and 17 schools offering courses in subjects that include medicine, computer engineering, and humanities.

The University is located on the coast of the Sea of Japan in Kanazawa – a city rich in history and culture. The city of Kanazawa has a highly respected intellectual profile since the time of the fiefdom (1598-1867). Kanazawa University is divided into two main campuses: Kakuma and Takaramachi for its approximately 10,200 students including 600 from overseas.

http://www.kanazawa-u.ac.jp/en/