title: Effect of plasmodial RESA protein on deformability of human red blood cells harboring Plasmodium falciparum.
abstract: During intraerythrocytic development, Plasmodium falciparum exports proteins that interact with the host cell plasma membrane and subplasma membrane-associated spectrin network. Parasite-exported proteins modify mechanical properties of host RBCs, resulting in altered cell circulation. In this work, optical tweezers experiments of cell mechanical properties at normal physiological and febrile temperatures are coupled, for the first time, with targeted gene disruption techniques to measure the effect of a single parasite-exported protein on host RBC deformability. We investigate Pf155/Ring-infected erythrocyte surface antigen (RESA), a parasite protein transported to the host spectrin network, on deformability of ring-stage parasite-harboring human RBCs. Using a set of parental, gene-disrupted, and revertant isogenic clones, we found that RESA plays a major role in reducing deformability of host cells at the early ring stage of parasite development, but not at more advanced stage. We also show that the effect of RESA on deformability is more pronounced at febrile temperature, which ring-stage parasite-harboring RBCs can be exposed to during a malaria attack, than at normal body temperature.
authors.affiliation: Department of Materials Science and Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: J P
authors.initials: JP
authors.lastname: Mills
authors.forename: M
authors.initials: M
authors.lastname: Diez-Silva
authors.forename: D J
authors.initials: DJ
authors.lastname: Quinn
authors.forename: M
authors.initials: M
authors.lastname: Dao
authors.forename: M J
authors.initials: MJ
authors.lastname: Lang
authors.forename: K S W
authors.initials: KS
authors.lastname: Tan
authors.forename: C T
authors.initials: CT
authors.lastname: Lim
authors.forename: G
authors.initials: G
authors.lastname: Milon
authors.forename: P H
authors.initials: PH
authors.lastname: David
authors.forename: O
authors.initials: O
authors.lastname: Mercereau-Puijalon
authors.forename: S
authors.initials: S
authors.lastname: Bonnefoy
authors.forename: S
authors.initials: S
authors.lastname: Suresh
mesh_terms: D000818:Animals; D048430:Cell Shape; D004912:Erythrocytes / Q000166:cytology* / Q000378:metabolism*; D006801:Humans; D010963:Plasmodium falciparum / Q000502:physiology*; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism*; D013696:Temperature; D053058:Trophozoites
chemical_list: D015800:Protozoan Proteins; C050256:ring-infected erythrocyte surface antigen (RESA), Plasmodium falciparum