Electric fields trigger ceramide-dependent vesicle budding and boost the generation of small extracellular vesicles
12 affiliations
- 1Department of Occupational and Environmental Health, School of Public Health and Nursing, Hangzhou Normal University, Hangzhou, China
- 2Zhejiang Key Laboratory of Geriatrics, Geriatrics Institute of Zhejiang Province, Zhejiang Hospital, Hangzhou, China
- 3Research Center for Industries of the Future, Westlake University, Hangzhou, China
- 4Material Science and Engineering, School of Engineering, Westlake University, Hangzhou, China
- 5School of Life Science, Westlake University, Hangzhou, China
- 6Department of Cancer Prevention, Zhejiang Cancer Hospital, Hangzhou, China
- 7Department of Nutrition and Toxicology, School of Public Health and Nursing, Hangzhou Normal University, Hangzhou, China
- 8Institute of Biomedical and Health Engineering, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China
- 9Key Laboratory of Reproductive Genetics, Department of Public Health, Zhejiang University School of Medicine, Zhejiang University, Ministry of Education, Hangzhou, China
- 10Department of Dermatology, School of Medicine, University of California, Davis, Davis, CA USA
- 11Department of Ophthalmology and Vision Science, School of Medicine, University of California, Davis, Davis, CA USA
- 12Center for Uterine Cancer Diagnosis and Therapy Research, The Affiliated Women’s Hospital, Zhejiang University School of Medicine, Hangzhou, China
Abstract
Small extracellular vesicles (sEVs) hold therapeutic promise, but clinical translation is limited by low yields. Physiological electric fields (EFs) naturally present during wound healing, embryonic development, and cancer progression—processes known to involve elevated production of sEVs. Here, we demonstrate that physiological-strength EFs (direct current, 50-200 mV/mm) dramatically enhance sEV secretion, achieving nearly 100-fold increases strength-dependently. Mechanistically, EFs augmented intraluminal vesicle formation within multivesicular bodies. Using giant plasma membrane vesicles, we observed EF-induced nanoscale vesicle formation, supporting an EF-driven membrane electroassembly and vesiculogenesis hypothesis. Notably, alternating current EFs (50 – 400 Hz) were 80-90% less effective than direct current EFs, highlighting membrane electropolarization-dependent modulation. Lipid raft/ceramide inhibition almost abolished EF-induced sEV secretion. Inhibition of the PI3K abolished approximately half of EF-triggered sEV release. Our findings not only unveil EFs as a potent physiological regulator of sEV secretion but also establish a biomimetic, high-yield production strategy leveraging bioelectric cues.
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BibTeX
@article{huang2026electric,
title = {{Electric fields trigger ceramide-dependent vesicle budding and boost the generation of small extracellular vesicles}},
author = {Shiwen Huang and Liangjing Chen and Chuan Sun and Runze Li and Yaojie Zhao and Jie Zhang and Liyan Zhai and Yue Zhang and Tianhui Chen and Yifei Cao and Qin Song and Xianrong Xu and Jianyun Zhang and Xiaohua Tan and Jiandong Wu and Guangdi Chen and Min Zhao and Jun Yang and Yan Zhang},
journal = {Communications Biology},
year = {2026},
month = jul,
doi = {10.1038/s42003-026-10526-z},
url = {https://doi.org/10.1038/s42003-026-10526-z},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Electric fields trigger ceramide-dependent vesicle budding and boost the generation of small extracellular vesicles
AU - Shiwen Huang
AU - Liangjing Chen
AU - Chuan Sun
AU - Runze Li
AU - Yaojie Zhao
AU - Jie Zhang
AU - Liyan Zhai
AU - Yue Zhang
AU - Tianhui Chen
AU - Yifei Cao
AU - Qin Song
AU - Xianrong Xu
AU - Jianyun Zhang
AU - Xiaohua Tan
AU - Jiandong Wu
AU - Guangdi Chen
AU - Min Zhao
AU - Jun Yang
AU - Yan Zhang
PY - 2026
DA - 2026/07/02
JO - Communications Biology
DO - 10.1038/s42003-026-10526-z
UR - https://doi.org/10.1038/s42003-026-10526-z
AB - Small extracellular vesicles (sEVs) hold therapeutic promise, but clinical translation is limited by low yields. Physiological electric fields (EFs) naturally present during wound healing, embryonic development, and cancer progression—processes known to involve elevated production of sEVs. Here, we demonstrate that physiological-strength EFs (direct current, 50-200 mV/mm) dramatically enhance sEV secretion, achieving nearly 100-fold increases strength-dependently. Mechanistically, EFs augmented intraluminal vesicle formation within multivesicular bodies. Using giant plasma membrane vesicles, we observed EF-induced nanoscale vesicle formation, supporting an EF-driven membrane electroassembly and vesiculogenesis hypothesis. Notably, alternating current EFs (50 – 400 Hz) were 80-90% less effective than direct current EFs, highlighting membrane electropolarization-dependent modulation. Lipid raft/ceramide inhibition almost abolished EF-induced sEV secretion. Inhibition of the PI3K abolished approximately half of EF-triggered sEV release. Our findings not only unveil EFs as a potent physiological regulator of sEV secretion but also establish a biomimetic, high-yield production strategy leveraging bioelectric cues.
SN - 2399-3642
ER -