title: Molecular mechanistic insights into the endothelial receptor mediated cytoadherence of Plasmodium falciparum-infected erythrocytes.
abstract: Cytoadherence or sequestration is essential for the pathogenesis of the most virulent human malaria species, Plasmodium falciparum (P. falciparum). Similar to leukocyte-endothelium interaction in response to inflammation, cytoadherence of P. falciparum infected red blood cells (IRBCs) to endothelium occurs under physiological shear stresses in blood vessels and involves an array of molecule complexes which cooperate to form stable binding. Here, we applied single-molecule force spectroscopy technique to quantify the dynamic force spectra and characterize the intrinsic kinetic parameters for specific ligand-receptor interactions involving two endothelial receptor proteins: thrombospondin (TSP) and CD36. It was shown that CD36 mediated interaction was much more stable than that mediated by TSP at single molecule level, although TSP-IRBC interaction appeared stronger than CD36-IRBC interaction in the high pulling rate regime. This suggests that TSP-mediated interaction may initiate cell adhesion by capturing the fast flowing IRBCs whereas CD36 functions as the 'holder' for providing stable binding.
authors: Singapore-MIT Alliance for Research & Technology, Singapore, Singapore.
authors: Ang
authors: A
authors: Li
authors: Tong Seng
authors: TS
authors: Lim
authors: Hui
authors: H
authors: Shi
authors: Jing
authors: J
authors: Yin
authors: Swee Jin
authors: SJ
authors: Tan
authors: Zhengjun
authors: Z
authors: Li
authors: Boon Chuan
authors: BC
authors: Low
authors: Kevin Shyong Wei
authors: KS
authors: Tan
authors: Chwee Teck
authors: CT
authors: Lim
mesh_terms: D018955:CD36 Antigens / Q000378:metabolism*; D002448:Cell Adhesion; D042783:Endothelial Cells / Q000378:metabolism*; D004912:Erythrocytes / Q000166:cytology* / Q000469:parasitology*; D006801:Humans; D007700:Kinetics; D018625:Microscopy, Atomic Force; D018613:Microscopy, Confocal; D010455:Peptides / Q000378:metabolism; D010963:Plasmodium falciparum / Q000502:physiology*; D013057:Spectrum Analysis; D013696:Temperature; D019699:Thrombospondins / Q000378:metabolism*
chemical_list: D018955:CD36 Antigens; D010455:Peptides; D019699:Thrombospondins