title: Clonal variants of Plasmodium falciparum exhibit a narrow range of rolling velocities to host receptor CD36 under dynamic flow conditions.
abstract: Cytoadhesion of Plasmodium falciparum parasitized red blood cells (pRBCs) has been implicated in the virulence of malaria infection. Cytoadhesive interactions are mediated by the protein family of Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1). The PfEMP1 family is under strong antibody and binding selection, resulting in extensive sequence and size variation of the extracellular domains. Here, we investigated cytoadhesion of pRBCs to CD36, a common receptor of P. falciparum field isolates, under dynamic flow conditions. Isogeneic parasites, predominantly expressing single PfEMP1 variants, were evaluated for binding to recombinant CD36 under dynamic flow conditions using microfluidic devices. We tested if PfEMP1 size (number of extracellular domains) or sequence variation affected the pRBC-CD36 interaction. Our analysis showed that clonal parasite variants varied ∼5-fold in CD36 rolling velocity despite extensive PfEMP1 sequence polymorphism. In addition, adherent pRBCs exhibited a characteristic hysteresis in rolling velocity at microvascular flow rates, which was accompanied by changes in pRBC shape and may represent important adaptations that favor stable binding.
authors.affiliation: Department of Chemistry, University of Washington, Seattle, Washington, USA.
authors.forename: Thurston
authors.initials: T
authors.lastname: Herricks
authors.forename: Marion
authors.initials: M
authors.lastname: Avril
authors.forename: Joel
authors.initials: J
authors.lastname: Janes
authors.forename: Joseph D
authors.initials: JD
authors.lastname: Smith
authors.forename: Pradipsinh K
authors.initials: PK
authors.lastname: Rathod
mesh_terms: D018955:CD36 Antigens / Q000378:metabolism*; D002448:Cell Adhesion; D006801:Humans; D044085:Microfluidics; D010963:Plasmodium falciparum / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D011110:Polymorphism, Genetic; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D015800:Protozoan Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D018955:CD36 Antigens; D015800:Protozoan Proteins; C085731:erythrocyte membrane protein 1, Plasmodium falciparum