Nanomechanics of Extracellular Vesicles Reveals Vesiculation Pathways

Raya Sorkin, Rick Huisjes, Filip Bošković, Daan Vorselen, Silvia Pignatelli, Yifat Ofir-Birin, Joames K. Freitas Leal, Jürgen Schiller, Debakshi Mullick, Wouter H. Roos, Giel Bosman, Neta Regev-Rudzki, Raymond M. Schiffelers, Gijs J.L. Wuite

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

Extracellular vesicles (EVs) are emerging as important mediators of cell–cell communication as well as potential disease biomarkers and drug delivery vehicles. However, the mechanical properties of these vesicles are largely unknown, and processes leading to microvesicle-shedding from the plasma membrane are not well understood. Here an in depth atomic force microscopy force spectroscopy study of the mechanical properties of natural EVs is presented. It is found that several natural vesicles of different origin have a different composition of lipids and proteins, but similar mechanical properties. However, vesicles generated by red blood cells (RBC) at different temperatures/incubation times are different mechanically. Quantifying the lipid content of EVs reveals that their stiffness decreases with the increase in their protein/lipid ratio. Further, by maintaining RBC at “extreme” nonphysiological conditions, the cells are pushed to utilize different vesicle generation pathways. It is found that RBCs can generate protein-rich soft vesicles, possibly driven by protein aggregation, and low membrane–protein content stiff vesicles, likely driven by cytoskeleton-induced buckling. Since similar cortical cytoskeleton to that of the RBC exists on the membranes of most mammalian cells, our findings help advancing the understanding of the fundamental process of vesicle generation.

Original languageEnglish
Article number1801650
Pages (from-to)1-8
Number of pages8
JournalSmall
Volume14
Issue number39
Early online date30 Aug 2018
DOIs
Publication statusPublished - 27 Sep 2018

Fingerprint

Nanomechanics
Lipids
Proteins
Blood
Erythrocytes
Cytoskeleton
Mechanical properties
Cell-Derived Microparticles
Cells
Atomic Force Microscopy
Biomarkers
Cell membranes
Drug delivery
Buckling
Atomic force microscopy
Spectrum Analysis
Agglomeration
Stiffness
Cell Membrane
Spectroscopy

Keywords

  • AFM
  • extracellular vesicles
  • membrane biophysics
  • RBC

Cite this

Sorkin, R., Huisjes, R., Bošković, F., Vorselen, D., Pignatelli, S., Ofir-Birin, Y., ... Wuite, G. J. L. (2018). Nanomechanics of Extracellular Vesicles Reveals Vesiculation Pathways. Small, 14(39), 1-8. [1801650]. https://doi.org/10.1002/smll.201801650
Sorkin, Raya ; Huisjes, Rick ; Bošković, Filip ; Vorselen, Daan ; Pignatelli, Silvia ; Ofir-Birin, Yifat ; Freitas Leal, Joames K. ; Schiller, Jürgen ; Mullick, Debakshi ; Roos, Wouter H. ; Bosman, Giel ; Regev-Rudzki, Neta ; Schiffelers, Raymond M. ; Wuite, Gijs J.L. / Nanomechanics of Extracellular Vesicles Reveals Vesiculation Pathways. In: Small. 2018 ; Vol. 14, No. 39. pp. 1-8.
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Sorkin, R, Huisjes, R, Bošković, F, Vorselen, D, Pignatelli, S, Ofir-Birin, Y, Freitas Leal, JK, Schiller, J, Mullick, D, Roos, WH, Bosman, G, Regev-Rudzki, N, Schiffelers, RM & Wuite, GJL 2018, 'Nanomechanics of Extracellular Vesicles Reveals Vesiculation Pathways' Small, vol. 14, no. 39, 1801650, pp. 1-8. https://doi.org/10.1002/smll.201801650

Nanomechanics of Extracellular Vesicles Reveals Vesiculation Pathways. / Sorkin, Raya; Huisjes, Rick; Bošković, Filip; Vorselen, Daan; Pignatelli, Silvia; Ofir-Birin, Yifat; Freitas Leal, Joames K.; Schiller, Jürgen; Mullick, Debakshi; Roos, Wouter H.; Bosman, Giel; Regev-Rudzki, Neta; Schiffelers, Raymond M.; Wuite, Gijs J.L.

In: Small, Vol. 14, No. 39, 1801650, 27.09.2018, p. 1-8.

Research output: Contribution to JournalArticleAcademicpeer-review

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AU - Sorkin, Raya

AU - Huisjes, Rick

AU - Bošković, Filip

AU - Vorselen, Daan

AU - Pignatelli, Silvia

AU - Ofir-Birin, Yifat

AU - Freitas Leal, Joames K.

AU - Schiller, Jürgen

AU - Mullick, Debakshi

AU - Roos, Wouter H.

AU - Bosman, Giel

AU - Regev-Rudzki, Neta

AU - Schiffelers, Raymond M.

AU - Wuite, Gijs J.L.

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N2 - Extracellular vesicles (EVs) are emerging as important mediators of cell–cell communication as well as potential disease biomarkers and drug delivery vehicles. However, the mechanical properties of these vesicles are largely unknown, and processes leading to microvesicle-shedding from the plasma membrane are not well understood. Here an in depth atomic force microscopy force spectroscopy study of the mechanical properties of natural EVs is presented. It is found that several natural vesicles of different origin have a different composition of lipids and proteins, but similar mechanical properties. However, vesicles generated by red blood cells (RBC) at different temperatures/incubation times are different mechanically. Quantifying the lipid content of EVs reveals that their stiffness decreases with the increase in their protein/lipid ratio. Further, by maintaining RBC at “extreme” nonphysiological conditions, the cells are pushed to utilize different vesicle generation pathways. It is found that RBCs can generate protein-rich soft vesicles, possibly driven by protein aggregation, and low membrane–protein content stiff vesicles, likely driven by cytoskeleton-induced buckling. Since similar cortical cytoskeleton to that of the RBC exists on the membranes of most mammalian cells, our findings help advancing the understanding of the fundamental process of vesicle generation.

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KW - AFM

KW - extracellular vesicles

KW - membrane biophysics

KW - RBC

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Sorkin R, Huisjes R, Bošković F, Vorselen D, Pignatelli S, Ofir-Birin Y et al. Nanomechanics of Extracellular Vesicles Reveals Vesiculation Pathways. Small. 2018 Sep 27;14(39):1-8. 1801650. https://doi.org/10.1002/smll.201801650