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Published on: May 16, 2013
Rosette margination in blood flow during malaria pathogenesis
Anil K Dasanna1, Marianne Papagrigorakes2, Michael Lanzer2
1Theoretical Physics of Living Matter, Institute for Advanced Simulation, Forschungszentrum Jülich, 52425 Jülich, Germany; Department of Physical Sciences, Indian Institute of Science Education and Research (IISER) Mohali, Sector 81, Knowledge City, Mohali 140306, India.
Abstract:
Margination is a physical phenomenon that describes the migration of cells and particles toward vessel walls in blood flow, and thus, it serves as a necessary precondition for the adhesion of particles suspended in blood plasma to the endothelium. In the context of malaria, adhesion of infected red blood cells (iRBCs) to the endothelium is essential for the disease progression, as iRBCs have to evade the removal from the blood circulation in the spleen. Some malaria strains lead to the formation of rosettes, multicellular structures composed of one iRBC surrounded by several adhered healthy RBCs (hRBCs). We employ mesoscopic hydrodynamics simulations and microfluidic experiments to investigate the margination of rosettes in blood flow at various flow rates, volume fractions of hRBCs, and binding strengths between iRBCs and hRBCs. Surprisingly, rosette margination is significantly weaker than that of single iRBCs, suggesting their limited adhesion potential in blood flow. The main reason for poor margination of rosettes is the deformability and dynamics of rosette clusters formed by several hRBCs around one iRBC. Simulation predictions are confirmed by microfluidic experiments. Our results suggest that the main function of rosette formation is not to enhance cytoadhesion to the endothelium, but to keep the iRBCs in the blood flow, at least along straight vessel segments.
Insights
Malaria rosettes, formed by infected red blood cells (iRBCs) and healthy red blood cells (hRBCs), show weaker margination than single iRBCs. This suggests rosette formation may keep iRBCs in blood flow rather than enhancing adhesion.
Area of Science:
- Biophysics
- Hematology
- Parasitology
Background:
- Margination describes cell migration to vessel walls, crucial for particle adhesion.
- In malaria, infected red blood cell (iRBC) adhesion to the endothelium is vital for disease progression and spleen evasion.
- Malaria can cause rosettes: iRBCs surrounded by healthy RBCs (hRBCs).
Purpose of the Study:
- To investigate the margination of malaria rosettes in blood flow.
- To compare rosette margination with single iRBC margination under varying conditions.
- To understand the role of rosette formation in iRBC behavior within blood circulation.
Main Methods:
- Mesoscopic hydrodynamics simulations were used to model rosette behavior.
- Microfluidic experiments were conducted to validate simulation predictions.
- Investigated effects of flow rates, hRBC volume fractions, and binding strengths.
Main Results:
- Rosette margination was surprisingly weaker than single iRBC margination.
- The deformability and dynamics of hRBCs within rosettes explain the reduced margination.
- Simulation predictions were consistent with experimental findings.
Conclusions:
- Rosette formation does not enhance cytoadhesion to the endothelium.
- Rosette formation may primarily function to maintain iRBCs within the blood flow, especially in straight vessels.
- Understanding margination dynamics is key to malaria pathogenesis.
