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

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  • Daan Vorselen

    (Vrije Universiteit Amsterdam
    University of Amsterdam and 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
    Rijksuniversiteit Groningen)

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.

Suggested Citation

  • 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 & Ric, 2018. "The fluid membrane determines mechanics of erythrocyte extracellular vesicles and is softened in hereditary spherocytosis," Nature Communications, Nature, vol. 9(1), pages 1-9, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-07445-x
    DOI: 10.1038/s41467-018-07445-x
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