title: Dynamic deformability of Plasmodium falciparum-infected erythrocytes exposed to artesunate in vitro.
abstract: Artesunate (ART) is widely used for the treatment of malaria, but the mechanisms of its effects on parasitized red blood cells (RBCs) are not fully understood. We investigated ART's influence on the dynamic deformability of ring-stage Plasmodium falciparum infected red blood cells (iRBCs) in order to elucidate its role in cellular mechanobiology. The dynamic deformability of RBCs was measured by passing them through a microfluidic device with repeated bottleneck structures. The quasi-static deformability measurement was performed using micropipette aspiration. After ART treatment, microfluidic experiments showed 50% decrease in iRBC transit velocity whereas only small (~10%) velocity reduction was observed among uninfected RBCs (uRBCs). Micropipette aspiration also revealed ART-induced stiffening in RBC membranes. These results demonstrate, for the first time, that ART reduces the dynamic and quasi-static RBC deformability, which may subsequently influence blood circulation through the microvasculature and spleen cordal meshwork, thus adding a new aspect to artesunate's mechanism of action.
authors.affiliation: Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
authors.forename: Sha
authors.initials: S
authors.lastname: Huang
authors.forename: Andreas
authors.initials: A
authors.lastname: Undisz
authors.forename: Monica
authors.initials: M
authors.lastname: Diez-Silva
authors.forename: Hansen
authors.initials: H
authors.lastname: Bow
authors.forename: Ming
authors.initials: M
authors.lastname: Dao
authors.forename: Jongyoon
authors.initials: J
authors.lastname: Han
mesh_terms: D000962:Antimalarials / Q000494:pharmacology; D037621:Artemisinins / Q000494:pharmacology*; D000077332:Artesunate; D002478:Cells, Cultured; D055119:Elastic Modulus / Q000187:drug effects / Q000502:physiology; D004912:Erythrocytes / Q000187:drug effects / Q000469:parasitology* / Q000502:physiology*; D006244:Hardness / Q000187:drug effects; D006801:Humans; D008560:Membrane Fluidity / Q000187:drug effects / Q000502:physiology*; D010963:Plasmodium falciparum / Q000502:physiology*
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D000077332:Artesunate