Microfluidic platform for automatic quantification of malaria parasite invasion under physiological flow conditions

Area of Science:

• Biophysics
• Parasitology
• Microfluidics

Background:

• Understanding blood flow forces on cellular processes is limited by experimental constraints.
• Plasmodium falciparum invasion of red blood cells is sensitive to shear stress, suggesting flow impacts parasite dynamics in vivo.
• Existing methods cannot assess the effects of flow-induced forces on parasite invasion.

Purpose of the Study:

• To develop and validate a microfluidic system for studying blood flow effects on Plasmodium falciparum invasion.
• To investigate the impact of flow conditions on parasite invasion rates in a genotype-dependent manner.

Main Methods:

• A four-channel microfluidic device mimicking post-capillary venules was designed with varying flow velocities.
• Highly synchronized Plasmodium falciparum parasites were introduced, and egress and invasion rates were quantified.
• Automated video analysis tracked cell identification and trajectories for precise quantification.

Main Results:

• The microfluidic device successfully quantified Plasmodium falciparum invasion under dynamic flow conditions.
• Deletion of erythrocyte binding antigen 175 (PfEBA175) significantly altered invasion rates under flow but not in static cultures.
• Flow conditions critically influence parasite invasion in a genotype-dependent manner.

Conclusions:

• Developed a novel microfluidic platform to study the impact of blood flow on parasite invasion.
• Demonstrated that flow-induced shear stress affects Plasmodium falciparum invasion, with genotype-specific effects.
• The methodology is applicable to other flow-dependent biological processes like cell adhesion and migration.