title: Febrile temperature leads to significant stiffening of Plasmodium falciparum parasitized erythrocytes.
abstract: Parasitic infection with Plasmodium falciparum is responsible for the most severe form of human malaria in which patients suffer from periodic fever. It is well established that during intra-erythrocytic maturation of the parasite in the red blood cell (RBC), the RBC becomes significantly more cytoadhesive and less deformable; these and other biochemical factors together with human host factors such as compromised immune status are important contributors to the disease pathology. There is currently substantial interest in understanding the loss of RBC deformability due to P. falciparum infection, but few results are available concerning effects of febrile conditions or parasitization on RBC membrane rheology. Here, for the first time, we report rheology of the single, isolated RBC with and without P. falciparum merozoite invasion, spanning a range from room temperature to febrile conditions (41 degrees C), over all the stages of parasite maturation. As expected, stiffness increased with parasite maturation. Surprisingly, however, stiffness increased acutely with temperature on a scale of minutes, particularly in late trophozoite and schizont stages. This acute stiffening in late falciparum stages may contribute to fever-dependent pathological consequences in the microcirculation.
authors.affiliation: Department of Environmental Health, Program in Molecular and Integrative Physiological Sciences, Harvard School of Public Health, 665 Huntington Ave., Boston, MA 02115, USA. mpuigdem@hsph.harvard.edu
authors.forename: Marina
authors.initials: M
authors.lastname: Marinkovic
authors.forename: Monica
authors.initials: M
authors.lastname: Diez-Silva
authors.forename: Ivan
authors.initials: I
authors.lastname: Pantic
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Fredberg
authors.forename: Subra
authors.initials: S
authors.lastname: Suresh
authors.forename: James P
authors.initials: JP
authors.lastname: Butler
mesh_terms: D000818:Animals; D004548:Elasticity; D004907:Erythrocyte Deformability; D004910:Erythrocyte Membrane / Q000469:parasitology* / Q000648:ultrastructure; D005334:Fever / Q000097:blood / Q000469:parasitology* / Q000473:pathology; D018056:Hemorheology; D006358:Hot Temperature; D006801:Humans; D008018:Life Cycle Stages; D008280:Magnetics; D008288:Malaria / Q000097:blood / Q000150:complications / Q000469:parasitology* / Q000473:pathology; D008855:Microscopy, Electron, Scanning; D010963:Plasmodium falciparum / Q000254:growth & development / Q000472:pathogenicity*; D013997:Time Factors; D014783:Viscosity