Microfluidic modeling of cell-cell interactions in malaria pathogenesis.
The clinical outcomes of human infections by Plasmodium falciparum remain highly unpredictable. A complete understanding of the complex interactions between host cells and the parasite will require in vitro experimental models that simultaneously capture diverse host-parasite interactions relevant to pathogenesis. Here we show that advanced microfluidic devices concurrently model (a) adhesion of infected red blood cells to host cell ligands, (b) rheological responses to changing dimensions of capillaries with shapes and sizes similar to small blood vessels, and (c) phagocytosis of infected erythrocytes by macrophages. All of this is accomplished under physiologically relevant flow conditions for up to 20 h. Using select examples, we demonstrate how this enabling technology can be applied in novel, integrated ways to dissect interactions between host cell ligands and parasitized erythrocytes in synthetic capillaries. The devices are cheap and portable and require small sample volumes; thus, they have the potential to be widely used in research laboratories and at field sites with access to fresh patient samples.
Antia
Meher
M
Department of Chemistry, University of Washington, Seattle, Washington, United States of America.
Herricks
Thurston
T
Rathod
Pradipsinh K
PK
D000818:Animals; D001783:Blood Flow Velocity; D016466:CHO Cells; D002448:Cell Adhesion / Q000502:physiology; D015815:Cell Adhesion Molecules; D002465:Cell Movement / Q000502:physiology; D006224:Cricetinae; D003412:Cricetulus; D004912:Erythrocytes / Q000378:metabolism / Q000469:parasitology; D006790:Host-Parasite Interactions; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism / Q000469:parasitology; D016778:Malaria, Falciparum / Q000469:parasitology*; D046210:Microfluidic Analytical Techniques; D008954:Models, Biological; D010587:Phagocytosis / Q000502:physiology; D010963:Plasmodium falciparum / Q000166:cytology / Q000472:pathogenicity / Q000502:physiology*; D014162:Transfection
D015815:Cell Adhesion Molecules; D018799:Intercellular Adhesion Molecule-1