The fluid membrane determines mechanics of erythrocyte extracellular vesicles and is softened in hereditary spherocytosis

Daan Vorselen, Susan M. van Dommelen, Raya Sorkin, Melissa C. Piontek, Jürgen Schiller, Sander T. Döpp, Sander A.A. Kooijmans, Brigitte A. van Oirschot, Birgitta A. Versluijs, Marc B. Bierings, Richard van Wijk, Raymond M. Schiffelers, Gijs J.L. Wuite, Wouter H. Roos

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

Extracellular vesicles (EVs) are widely studied regarding their role in cell-to-cell communication and disease, as well as for applications as biomarkers or drug delivery vehicles. EVs contain membrane and intraluminal proteins, affecting their structure and thereby likely their functioning. Here, we use atomic force microscopy for mechanical characterization of erythrocyte, or red blood cell (RBC), EVs from healthy individuals and from patients with hereditary spherocytosis (HS) due to ankyrin deficiency. While these EVs are packed with proteins, their response to indentation resembles that of fluid liposomes lacking proteins. The bending modulus of RBC EVs of healthy donors is ~15 kbT, similar to the RBC membrane. Surprisingly, whereas RBCs become more rigid in HS, patient EVs have a significantly (~40%) lower bending modulus than donor EVs. These results shed light on the mechanism and effects of EV budding and might explain the reported increase in vesiculation of RBCs in HS patients.

Original languageEnglish
Article number4960
Pages (from-to)1-9
Number of pages9
JournalNature Communications
Volume9
DOIs
Publication statusPublished - 23 Nov 2018

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Hereditary Spherocytosis
erythrocytes
Mechanics
Blood
Erythrocytes
membranes
Membranes
Fluids
fluids
proteins
Ankyrins
Biomarkers
Cell membranes
Drug delivery
Indentation
Liposomes
biomarkers
Atomic force microscopy
Membrane Proteins
Proteins

Cite this

Vorselen, Daan ; van Dommelen, Susan M. ; Sorkin, Raya ; Piontek, Melissa C. ; Schiller, Jürgen ; Döpp, Sander T. ; Kooijmans, Sander A.A. ; van Oirschot, Brigitte A. ; Versluijs, Birgitta A. ; Bierings, Marc B. ; van Wijk, Richard ; Schiffelers, Raymond M. ; Wuite, Gijs J.L. ; Roos, Wouter H. / The fluid membrane determines mechanics of erythrocyte extracellular vesicles and is softened in hereditary spherocytosis. In: Nature Communications. 2018 ; Vol. 9. pp. 1-9.
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abstract = "Extracellular vesicles (EVs) are widely studied regarding their role in cell-to-cell communication and disease, as well as for applications as biomarkers or drug delivery vehicles. EVs contain membrane and intraluminal proteins, affecting their structure and thereby likely their functioning. Here, we use atomic force microscopy for mechanical characterization of erythrocyte, or red blood cell (RBC), EVs from healthy individuals and from patients with hereditary spherocytosis (HS) due to ankyrin deficiency. While these EVs are packed with proteins, their response to indentation resembles that of fluid liposomes lacking proteins. The bending modulus of RBC EVs of healthy donors is ~15 kbT, similar to the RBC membrane. Surprisingly, whereas RBCs become more rigid in HS, patient EVs have a significantly (~40{\%}) lower bending modulus than donor EVs. These results shed light on the mechanism and effects of EV budding and might explain the reported increase in vesiculation of RBCs in HS patients.",
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Vorselen, D, van Dommelen, SM, Sorkin, R, Piontek, MC, Schiller, J, Döpp, ST, Kooijmans, SAA, van Oirschot, BA, Versluijs, BA, Bierings, MB, van Wijk, R, Schiffelers, RM, Wuite, GJL & Roos, WH 2018, 'The fluid membrane determines mechanics of erythrocyte extracellular vesicles and is softened in hereditary spherocytosis' Nature Communications, vol. 9, 4960, pp. 1-9. https://doi.org/10.1038/s41467-018-07445-x

The fluid membrane determines mechanics of erythrocyte extracellular vesicles and is softened in hereditary spherocytosis. / Vorselen, Daan; van Dommelen, Susan M.; Sorkin, Raya; Piontek, Melissa C.; Schiller, Jürgen; Döpp, Sander T.; Kooijmans, Sander A.A.; van Oirschot, Brigitte A.; Versluijs, Birgitta A.; Bierings, Marc B.; van Wijk, Richard; Schiffelers, Raymond M.; Wuite, Gijs J.L.; Roos, Wouter H.

In: Nature Communications, Vol. 9, 4960, 23.11.2018, p. 1-9.

Research output: Contribution to JournalArticleAcademicpeer-review

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AU - Schiller, Jürgen

AU - Döpp, Sander T.

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AU - van Oirschot, Brigitte A.

AU - Versluijs, Birgitta A.

AU - Bierings, Marc B.

AU - van Wijk, Richard

AU - Schiffelers, Raymond M.

AU - Wuite, Gijs J.L.

AU - Roos, Wouter H.

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