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

Daan Vorselen, Susan M. Dommelen, Raya Sorkin, Melissa C. Piontek, Jürgen Schiller, Sander T. Döpp, Sander A. A. Kooijmans, Brigitte A. Oirschot, Birgitta A. Versluijs, Marc B. Bierings, Richard Wijk, Raymond M. Schiffelers, Gijs J. L. Wuite () and Wouter H. Roos ()
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Daan Vorselen: Vrije Universiteit Amsterdam
Susan M. Dommelen: University Medical Center Utrecht, Utrecht University
Raya Sorkin: Vrije Universiteit Amsterdam
Melissa C. Piontek: Rijksuniversiteit Groningen
Jürgen Schiller: University of Leipzig, Medical Faculty
Sander T. Döpp: Vrije Universiteit Amsterdam
Sander A. A. Kooijmans: University Medical Center Utrecht, Utrecht University
Brigitte A. Oirschot: University Medical Center Utrecht, Utrecht University
Birgitta A. Versluijs: University Medical Center Utrecht
Marc B. Bierings: University Medical Center Utrecht
Richard Wijk: University Medical Center Utrecht, Utrecht University
Raymond M. Schiffelers: University Medical Center Utrecht, Utrecht University
Gijs J. L. Wuite: Vrije Universiteit Amsterdam
Wouter H. Roos: Vrije Universiteit Amsterdam

Nature Communications, 2018, vol. 9, issue 1, 1-9

Abstract: 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.

Date: 2018
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DOI: 10.1038/s41467-018-07445-x

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