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

• DOI: 10.1038/s41467-018-07445-x
• Publication Date: 2018-11-19T16:20:56Z
• Authors: Daan Vorselen; Susan M. van Domm...; Raya Sorkin; Melissa C. Piontek; Jürgen Schiller; Sander T. Döpp; Sander A. A. Kooi...; Brigitte A. van O...; Birgitta A. Versl...; Marc B. Bierings; Richard van Wijk; Raymond M. Schiff...; Gijs J. L. Wuite; Wouter H. Roos
• Keywords: 0301 basic medicine; Erythrocytes; Membrane Fluidity; Science; General Biochemistry,Genetics and Molecular Biology; Q; Erythrocyte Membrane; General Physics and Astronomy; Proteins; General Chemistry; Spherocytosis, Hereditary; Microscopy, Atomic Force; Article; 3. Good health; Extracellular Vesicles; 03 medical and health sciences; SDG 3 - Good Health and Well-being; Humans

AbstractExtracellular 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.