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Rosette margination in blood flow during malaria pathogenesis.

Anil K Dasanna1, Marianne Papagrigorakes2, Michael Lanzer2

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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.

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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.