Knob architecture and hemoglobin composition shape recovery dynamics of Plasmodium falciparum-infected erythrocytes
- 1Heidelberg University
Abstract
The deformability of the red blood cell (RBC) is essential for microcirculatory flow and is profoundly altered in hemoglobinopathies and during infection with Plasmodium falciparum. While many mechanical tests have been developed to probe RBC-mechanics, the dynamics of cell shape recovery following large deformations remains poorly characterized. Here, we integrate microfluidic constriction assays, ultrafast imaging, and computer simulations to quantify time-resolved shape recovery of individual erythrocytes. We show that parasite infection is the primary determinant of RBC viscoelastic behavior. In wild-type (HbAA) erythrocytes, the relaxation time increases progressively from ring to trophozoite to schizont stages, consistent with parasite-induced membrane stiffening and enhanced membrane-cytoskeleton coupling. In contrast, sickle trait (HbAS) erythrocytes exhibit a distinct response: although deformation becomes increasingly irreversible during parasite maturation, the relaxation time after constriction remains largely unchanged. Analysis of a mutant parasite line with enlarged and sparsely distributed knobs revealed a significant increase in relaxation time, demonstrating that knob architecture modulates recovery kinetics. Together, these findings suggest that the coupling between membrane and cytoskeleton, which is strongly changed by the establishment of the knobs during an infection with Plasmodium falciparum, should have a strong detrimental effect on microcirculatory flow, which is however weakened by the sickle cell trait.
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BibTeX
@misc{tanaka2026knob,
title = {{Knob architecture and hemoglobin composition shape recovery dynamics of Plasmodium falciparum-infected erythrocytes}},
author = {M. Tanaka and M. Lanzer and J. czajor and V. Lengyel and C. Sanchez and S. Dammrich and F. Hamprecht and A. Dasanna and P. Ruppert and L. Lettermann and D. A. Fedosov and U. S. Schwarz},
howpublished = {bioRxiv},
year = {2026},
month = aug,
doi = {10.64898/2026.08.26.747262},
url = {https://www.biorxiv.org/content/10.64898/2026.08.26.747262v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Knob architecture and hemoglobin composition shape recovery dynamics of Plasmodium falciparum-infected erythrocytes
AU - M. Tanaka
AU - M. Lanzer
AU - J. czajor
AU - V. Lengyel
AU - C. Sanchez
AU - S. Dammrich
AU - F. Hamprecht
AU - A. Dasanna
AU - P. Ruppert
AU - L. Lettermann
AU - D. A. Fedosov
AU - U. S. Schwarz
PY - 2026
DA - 2026/08/26
PB - bioRxiv
DO - 10.64898/2026.08.26.747262
UR - https://www.biorxiv.org/content/10.64898/2026.08.26.747262v1
AB - The deformability of the red blood cell (RBC) is essential for microcirculatory flow and is profoundly altered in hemoglobinopathies and during infection with Plasmodium falciparum. While many mechanical tests have been developed to probe RBC-mechanics, the dynamics of cell shape recovery following large deformations remains poorly characterized. Here, we integrate microfluidic constriction assays, ultrafast imaging, and computer simulations to quantify time-resolved shape recovery of individual erythrocytes. We show that parasite infection is the primary determinant of RBC viscoelastic behavior. In wild-type (HbAA) erythrocytes, the relaxation time increases progressively from ring to trophozoite to schizont stages, consistent with parasite-induced membrane stiffening and enhanced membrane-cytoskeleton coupling. In contrast, sickle trait (HbAS) erythrocytes exhibit a distinct response: although deformation becomes increasingly irreversible during parasite maturation, the relaxation time after constriction remains largely unchanged. Analysis of a mutant parasite line with enlarged and sparsely distributed knobs revealed a significant increase in relaxation time, demonstrating that knob architecture modulates recovery kinetics. Together, these findings suggest that the coupling between membrane and cytoskeleton, which is strongly changed by the establishment of the knobs during an infection with Plasmodium falciparum, should have a strong detrimental effect on microcirculatory flow, which is however weakened by the sickle cell trait.
ER -