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Published on: May 16, 2013
Rolling Adhesion of Schizont Stage Malaria-Infected Red Blood Cells in Shear Flow
Anil K Dasanna1, Christine Lansche2, Michael Lanzer2
1BioQuant-Center for Quantitative Biology, Heidelberg University, Heidelberg, Germany; Institute of Theoretical Physics, Heidelberg University, Heidelberg, Germany.
Abstract:
To avoid clearance by the spleen, red blood cells infected with the human malaria parasite Plasmodium falciparum (iRBCs) adhere to the vascular endothelium through adhesive protrusions called "knobs" that the parasite induces on the surface of the host cell. However, the detailed relation between the developing knob structure and the resulting movement in shear flow is not known. Using flow chamber experiments on endothelial monolayers and tracking of the parasite inside the infected host cell, we find that trophozoites (intermediate-stage iRBCs) tend to flip due to their biconcave shape, whereas schizonts (late-stage iRBCs) tend to roll due to their almost spherical shape. We then use adhesive dynamics simulations for spherical cells to predict the effects of knob density and receptor multiplicity per knob on rolling adhesion of schizonts. We find that rolling adhesion requires a homogeneous coverage of the cell surface by knobs and that rolling adhesion becomes more stable and slower for higher knob density. Our experimental data suggest that schizonts are at the border between transient and stable rolling adhesion. They also allow us to establish an estimate for the molecular parameters for schizont adhesion to the vascular endothelium and to predict bond dynamics in the contact region.
Insights
Malaria parasites (Plasmodium falciparum) in red blood cells use "knobs" to stick to blood vessels. Knob density affects how infected cells roll, with higher density leading to slower, more stable adhesion.
Area of Science:
- Biophysics
- Parasitology
- Cellular Biology
Background:
- Infected red blood cells (iRBCs) adhere to the endothelium via parasite-induced knobs to evade spleen clearance.
- The relationship between knob development and iRBC behavior in shear flow is not fully understood.
Purpose of the Study:
- To investigate the relationship between knob structure and the movement of Plasmodium falciparum-infected red blood cells in shear flow.
- To determine the effects of knob density and receptor multiplicity on the rolling adhesion of schizont-stage iRBCs.
Main Methods:
- Flow chamber experiments on endothelial monolayers.
- Tracking of infected red blood cells (iRBCs) within the host cell.
- Adhesive dynamics simulations for spherical cells.
Main Results:
- Trophozoite-stage iRBCs tend to flip due to their biconcave shape.
- Schizont-stage iRBCs tend to roll due to their nearly spherical shape.
- Rolling adhesion requires homogeneous knob coverage; higher knob density increases stability and decreases speed.
- Schizonts exhibit characteristics of both transient and stable rolling adhesion.
Conclusions:
- Knob density and distribution are critical for the rolling adhesion dynamics of malaria-infected red blood cells.
- The study provides molecular parameter estimates for schizont adhesion and predicts bond dynamics.
- Understanding these mechanisms is crucial for developing strategies to combat malaria pathogenesis.
