Quantifying the Shape and Stiffness of Single Extracellular Vesicles in Aqueous Solution via Membrane Diffusivity Measurements
Quantifying the shape and stiffness of extracellular vesicles (EVs) is essential for understanding their biophysical properties and roles in intercellular communication. However, achieving single-particle resolution under physiological conditions remains a significant challenge. Here, we introduce an approach that integrates single-molecule diffusivity mapping (SM<i>d</i>M) with diffusion models for spherical and discoidal shapes to quantify the geometric and mechanical properties of individual liposomes and EVs in aqueous solution. Our findings identify charged lipids and cholesterol as critical factors that enhance liposome stiffness, driving their shapes closer to spheres. Applying this method to EVs reveals that those derived from tumor cells exhibit lower stiffness compared to EVs from normal cells, consistent with the biomechanical characteristics of their parent cells. This rapid, high-throughput strategy for characterizing the shape and stiffness of single EVs in aqueous solution offers promising applications in cancer biomarker discovery and the development of EV-based therapeutics.
Authors
- Feiyang Cheng (ORCID: https://orcid.org/0000-0002-3933-8880)
- Limin Xiang (ORCID: https://orcid.org/0000-0003-1488-2705)
- Xiang Zhan (ORCID: https://orcid.org/0000-0003-0756-2359)
- Wei‐Hua Huang (ORCID: https://orcid.org/0000-0001-8951-075X)
- Wei Yan (ORCID: https://orcid.org/0000-0003-3978-7675)
- Chu Han (ORCID: https://orcid.org/0000-0001-8848-7391)
- Hong Fan (ORCID: https://orcid.org/0000-0003-3389-6213)
- Mengyao Zhang (ORCID: https://orcid.org/0009-0009-6545-8171)
- Xiao Hui Zhang (ORCID: https://orcid.org/0000-0002-8778-595X)
- Jing Zhang (ORCID: https://orcid.org/0000-0001-6438-9113)
- Liu Liu (ORCID: https://orcid.org/0000-0002-3641-5297)
- Yihan Wang (ORCID: https://orcid.org/0000-0002-4847-6986)
- Huihui Gao
- Xinwei Zhang (ORCID: https://orcid.org/0000-0003-3325-5010)
- Yan‐Ling Liu (ORCID: https://orcid.org/0000-0002-7386-354X)
- Hao Ge (ORCID: https://orcid.org/0000-0002-2775-5564)
- Wei Zhang (ORCID: https://orcid.org/0000-0001-7005-5726)
- Jingwen Deng
- Zirui Zhou (ORCID: https://orcid.org/0000-0002-9202-2180)
Institutions
- Peking University (CN)
- Wuhan University (CN)
- Zhongnan Hospital of Wuhan University (CN)
- Center for Life Sciences (CN)
- Imaging Center (US)
Publication Details
- Journal
- Chemical & Biomedical Imaging
- Published
- 2025-04-09
- DOI
- https://doi.org/10.1021/cbmi.5c00011
- Primary Topic
- Extracellular vesicles in disease
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Natural Science Foundation of China
- National Key Research and Development Program of China
- Fundamental Research Funds for the Central Universities
- Renmin Hospital of Wuhan University