Force spectroscopy reveals membrane fluctuations and surface adhesion of extracellular nanovesicles impact their elastic behavior

The elastic properties of nanoscale extracellular vesicles (EVs) are believed to influence their cellular interactions, thus having a profound implication in intercellular communication. However, accurate quantification of their elastic modulus is challenging due to their nanoscale dimensions and their fluid-like lipid bilayer. We show that the previous attempts to develop atomic force microscopy-based protocol are flawed as they lack theoretical underpinning as well as ignore important contributions arising from the surface adhesion forces and membrane fluctuations. We develop a protocol comprising a theoretical framework, experimental technique, and statistical approach to accurately quantify the bending and elastic modulus of EVs. The method reveals that membrane fluctuations play a dominant role even for a single EV. The method is then applied to EVs derived from human embryonic kidney cells and their genetically engineered classes altering the tetraspanin expression. The data show a large spread; the area modulus is in the range of 4 to 19 mN/m and the bending modulus is in the range of 15 to 33 [Formula: see text], respectively. Surprisingly, data for a single EV, revealed by repeated measurements, also show a spread that is attributed to their compositionally heterogeneous fluid membrane and thermal effects. Our protocol uncovers the influence of membrane protein alterations on the elastic modulus of EVs.

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Publication Details

Journal
Proceedings of the National Academy of Sciences
Published
2025-04-18
DOI
https://doi.org/10.1073/pnas.2414174122
Citations
2
Primary Topic
Extracellular vesicles in disease
Type
article
Field-Weighted Citation Impact
1.61

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article

Force spectroscopy reveals membrane fluctuations and surface adhesion of extracellular nanovesicles impact their elastic behavior

André Görgens, Prattakorn Metem, Dhrubaditya Mitra, Fredrik Stridfeldt et al.
2 citations
Proceedings of the National Academy of Sciences
Extracellular vesicles in disease
1.61
article

Force spectroscopy reveals membrane fluctuations and surface adhesion of extracellular nanovesicles impact their elastic behavior

André Görgens, Prattakorn Metem, Dhrubaditya Mitra, Fredrik Stridfeldt, Apurba Dev, Doste R. Mamand, Moein Talebian Gevari, Margaret N. Holme, Vikash Pandey, Hanna Kylhammar, Vipin Agrawal, Samir EL Andaloussi, Oskar Gustafsson, Jennifer Gilbert, Lukas Palmgren
article en
2 citations

Abstract

The elastic properties of nanoscale extracellular vesicles (EVs) are believed to influence their cellular interactions, thus having a profound implication in intercellular communication. However, accurate quantification of their elastic modulus is challenging due to their nanoscale dimensions and their fluid-like lipid bilayer. We show that the previous attempts to develop atomic force microscopy-based protocol are flawed as they lack theoretical underpinning as well as ignore important contributions arising from the surface adhesion forces and membrane fluctuations. We develop a protocol comprising a theoretical framework, experimental technique, and statistical approach to accurately quantify the bending and elastic modulus of EVs. The method reveals that membrane fluctuations play a dominant role even for a single EV. The method is then applied to EVs derived from human embryonic kidney cells and their genetically engineered classes altering the tetraspanin expression. The data show a large spread; the area modulus is in the range of 4 to 19 mN/m and the bending modulus is in the range of 15 to 33 [Formula: see text], respectively. Surprisingly, data for a single EV, revealed by repeated measurements, also show a spread that is attributed to their compositionally heterogeneous fluid membrane and thermal effects. Our protocol uncovers the influence of membrane protein alterations on the elastic modulus of EVs.

Proceedings of the National Academy of SciencesVol. 122(16)
Uppsala University (SE), Karolinska University Hospital (SE), Stockholm University (SE), Karolinska Institutet (SE), Institute for Transfusion Medicine (US), Essen University Hospital (DE), Breast Center (CH), Center of Research and Technologic Development in Electrochemistry (MX), Cellular Research (United States) (US), Futura Medical (United Kingdom) (GB), U-M Rogel Cancer Center (US), University of Duisburg-Essen (DE), Chalmers University of Technology (SE), KTH Royal Institute of Technology (SE)
Stockholm läns landsting
Openalex Percentile: Top 18%
Extracellular vesicles in disease
1.61
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