TY  - JOUR
A1  - Shirakashi, Ryo
A1  - Sisario, Dmitri
A1  - Taban, Danush
A1  - Korsa, Tessa
A1  - Wanner, Sophia B.
A1  - Neubauer, Julia
A1  - Djuzenova, Cholpon S.
A1  - Zimmermann, Heiko
A1  - Sukhorukov, Vladimir L.
T1  - Contraction of the rigor actomyosin complex drives bulk hemoglobin expulsion from hemolyzing erythrocytes
JF  - Biomechanics and Modeling in Mechanobiology
N2  - Erythrocyte ghost formation via hemolysis is a key event in the physiological clearance of senescent red blood cells (RBCs) in the spleen. The turnover rate of millions of RBCs per second necessitates a rapid efflux of hemoglobin (Hb) from RBCs by a not yet identified mechanism. Using high-speed video-microscopy of isolated RBCs, we show that electroporation-induced efflux of cytosolic ATP and other small solutes leads to transient cell shrinkage and echinocytosis, followed by osmotic swelling to the critical hemolytic volume. The onset of hemolysis coincided with a sudden self-propelled cell motion, accompanied by cell contraction and Hb-jet ejection. Our biomechanical model, which relates the Hb-jet-driven cell motion to the cytosolic pressure generation via elastic contraction of the RBC membrane, showed that the contributions of the bilayer and the bilayer-anchored spectrin cytoskeleton to the hemolytic cell motion are negligible. Consistent with the biomechanical analysis, our biochemical experiments, involving extracellular ATP and the myosin inhibitor blebbistatin, identify the low abundant non-muscle myosin 2A (NM2A) as the key contributor to the Hb-jet emission and fast hemolytic cell motion. Thus, our data reveal a rapid myosin-based mechanism of hemolysis, as opposed to a much slower diffusive Hb efflux.
KW  - electroporation
KW  - cell velocimetry
KW  - hemoglobin jet
KW  - non-muscle myosin
KW  - echinocytes
KW  - cytoskeleton
Y1  - 2023
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-325107
VL  - 22
IS  - 2
ER  -