title: Cytoadhesion of Plasmodium falciparum-infected erythrocytes to chondroitin-4-sulfate is cooperative and shear enhanced.
abstract: Infections with the human malaria parasite Plasmodium falciparum during pregnancy can lead to severe complications for both mother and child, resulting from the cytoadhesion of parasitized erythrocytes in the intervillous space of the placenta. Cytoadherence is conferred by the specific interaction of the parasite-encoded adhesin VAR2CSA with chondroitin-4-sulfate (CSA) present on placental proteoglycans. CSA presented elsewhere in the microvasculature does not afford VAR2CSA-mediated cytoadhesion of parasitized erythrocytes. To address the placenta-specific binding tropism, we investigated the effect of the receptor/ligand arrangement on cytoadhesion, using artificial membranes with different CSA spacing intervals. We found that cytoadhesion is strongly dependent on the CSA distance, with half-maximal adhesion occurring at a CSA distance of 9 ± 1 nm at all hydrodynamic conditions. Moreover, binding to CSA was cooperative and shear stress induced. These findings suggest that the CSA density, together with allosteric effects in VAR2CSA, aid in discriminating between different CSA milieus.
authors.affiliation: Department of Infectious Diseases, Parasitology, and Institute of Physical Chemistry, Physical Chemistry of Biosystems, Heidelberg University, Heidelberg, Germany;
authors.forename: Harden
authors.initials: H
authors.lastname: Rieger
authors.affiliation: Institute of Physical Chemistry, Physical Chemistry of Biosystems, Heidelberg University, Heidelberg, Germany; Department of Chemistry, Saitama University, Saitama, Japan;
authors.forename: Hiroshi Y
authors.initials: HY
authors.lastname: Yoshikawa
authors.affiliation: Department of Infectious Diseases, Parasitology, and.
authors.forename: Katharina
authors.initials: K
authors.lastname: Quadt
authors.affiliation: Center for Medical Parasitology, University of Copenhagen, Copenhagen, Denmark; and.
authors.forename: Morten A
authors.initials: MA
authors.lastname: Nielsen
authors.affiliation: Department of Infectious Diseases, Parasitology, and.
authors.forename: Cecilia P
authors.initials: CP
authors.lastname: Sanchez
authors.affiliation: Center for Medical Parasitology, University of Copenhagen, Copenhagen, Denmark; and.
authors.forename: Ali
authors.initials: A
authors.lastname: Salanti
authors.affiliation: Institute of Physical Chemistry, Physical Chemistry of Biosystems, Heidelberg University, Heidelberg, Germany; Institute for Integrated Cell-Material Science, Kyoto University, Kyoto, Japan.
authors.forename: Motomu
authors.initials: M
authors.lastname: Tanaka
authors.affiliation: Department of Infectious Diseases, Parasitology, and.
authors.forename: Michael
authors.identifier: http://orcid.org/0000-0002-0220-6526
authors.initials: M
authors.lastname: Lanzer
mesh_terms: D002448:Cell Adhesion / Q000502:physiology*; D002809:Chondroitin Sulfates / Q000378:metabolism*; D004912:Erythrocytes / Q000378:metabolism / Q000469:parasitology*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008051:Lipid Bilayers / Q000378:metabolism; D016778:Malaria, Falciparum / Q000469:parasitology*; D018625:Microscopy, Atomic Force; D011247:Pregnancy; D015597:Pregnancy Complications, Parasitic / Q000469:parasitology*
chemical_list: D008051:Lipid Bilayers; D002809:Chondroitin Sulfates