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Simulation of malaria-infected red blood cells in microfluidic channels: Passage and blockage
1Department of Chemical and Biological Engineering, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada.
Abstract:
Malaria-infected red blood cells (iRBCs) become less deformable with the progression of infection and tend to occlude microcapillaries. This process has been investigated in vitro using microfluidic channels. The objective of this paper is to provide a quantitative basis for interpreting the experimental observations of iRBC occlusion of microfluidic channels. Using a particle-based model for the iRBC, we simulate the traverse of iRBCs through a converging microfluidic channel and explore the progressive loss of cell deformability due to three factors: the stiffening of the membrane, the reduction of the cell's surface-volume ratio, and the growing solid parasites inside the cell. When examined individually, each factor tends to hinder the passage of the iRBC and lengthen the transit time. Moreover, at sufficient magnitude, each may lead to obstruction of narrow microfluidic channels. We then integrate the three factors into a series of simulations that mimic the development of malaria infection through the ring, trophozoite, and schizont stages. These simulations successfully reproduce the experimental observation that with progression of infection, the iRBC transitions from passage to blockage in larger and larger channels. The numerical results suggest a scheme for quantifying iRBC rigidification through microfluidic measurements of the critical pressure required for passage.
Insights
Malaria-infected red blood cells (iRBCs) become less deformable and block microfluidic channels as infection progresses. This study quantifies how membrane stiffening, reduced surface-volume ratio, and parasite growth contribute to iRBC occlusion.
Area of Science:
- Biophysics
- Computational Biology
- Infectious Disease Modeling
Background:
- Malaria-infected red blood cells (iRBCs) exhibit reduced deformability, leading to microcapillary occlusion.
- Understanding iRBC mechanics is crucial for comprehending malaria pathogenesis and developing treatments.
Purpose of the Study:
- To develop a quantitative model for iRBC occlusion in microfluidic channels.
- To elucidate the contributions of specific factors to iRBC mechanical changes during malaria infection.
Main Methods:
- Particle-based modeling of iRBCs traversing converging microfluidic channels.
- Simulation of deformability loss due to membrane stiffening, altered surface-volume ratio, and intracellular parasite growth.
- Integration of these factors to mimic different malaria parasite stages (ring, trophozoite, schizont).
Main Results:
- Each simulated factor (membrane stiffening, reduced surface-volume ratio, parasite growth) individually hinders iRBC passage and increases transit time.
- Combined factors successfully replicate experimental observations of iRBCs transitioning from passage to blockage in progressively larger channels.
- Simulations demonstrate that increasing infection severity correlates with increased channel blockage.
Conclusions:
- The study provides a quantitative framework for interpreting iRBC occlusion in microfluidics.
- A method for quantifying iRBC rigidification using microfluidic critical pressure measurements is proposed.
- The findings offer insights into malaria-induced changes in red blood cell mechanics and potential diagnostic approaches.
