The sickle cell trait affects contact dynamics and endothelial cell activation in Plasmodium falciparum -infected erythrocytes

Communications Biology

Motomu Tanaka¹  Cecilia P. Sanchez²  Benoit Gamain³  Bernd Buchholz⁴  Marilou Té⁵  Benjamin Frö⁷  Christine Lansche⁷  Katharina Quadt⁹  Dimitris Missirlis^1,10  tard^1,11  Michael Lanzer^1,12  Ulrich S. Schwarz^1,13  hlich^1,15  Anil K. Dasanna^1,15 

[1]Biologie Inté

[2]Paris Diderot, Inserm, INTS, Unité

[3]Sorbonne Paris Cité

[4], Université

[5]Department of Cellular Biophysics, Max Planck Institute for Medical Research, Heidelberg, Germany

[6]Department of Hematology and Oncology, University Children’

[7]Department of Infectious Diseases, Parasitology, Universitä

[8]Excellence GR-Ex, Paris, France

[9]Institute for Theoretical Physics and BioQuant-Center for Quantitative Biology, Heidelberg University, Heidelberg, Germany

[10]Physical Chemistry of Biosystems, University of Heidelberg, Heidelberg, Germany

[11]Université

[12]e du Globule Rouge, UMR S1134, Severe Malaria Pathogenesis Group, Laboratoire d’

[13]gré

[14]s Hospital, Medical Faculty Mannheim, Mannheim, Germany

[15]tsklinikum Heidelberg, Heidelberg, Germany

DOI  :  10.1038/s42003-018-0223-3

学科分类：生物科学（综合）

来源: Nature Publishing Group

【 摘 要 】

Sickle cell trait, a common hereditary blood disorder, protects carriers from severe disease in infections with the human malaria parasite Plasmodium falciparum. Protection is associated with a reduced capacity of parasitized erythrocytes to cytoadhere to the microvascular endothelium and cause vaso-occlusive events. However, the underpinning cellular and biomechanical processes are only partly understood and the impact on endothelial cell activation is unclear. Here, we show, by combining quantitative flow chamber experiments with multiscale computer simulations of deformable cells in hydrodynamic flow, that parasitized erythrocytes containing the sickle cell haemoglobin displayed altered adhesion dynamics, resulting in restricted contact footprints on the endothelium. Main determinants were cell shape, knob density and membrane bending. As a consequence, the extent of endothelial cell activation was decreased. Our findings provide a quantitative understanding of how the sickle cell trait affects the dynamic cytoadhesion behavior of parasitized erythrocytes and, in turn, endothelial cell activation.

【 授权许可】

CC BY