A promising strategy to target malaria

In “Demonstration of specific binding of heparin to Plasmodium falciparum-infected vs non-infected red blood cells by single-molecule force spectroscopy”, by Valle-Delgado, Urbán and Fernàndez-Busquets, published in the latest edition of Nanoscale, the researchers focused on the changes to the structure of red blood cells (RBCs) infected with the malaria parasite Plasmodium falciparum.

Image: The adhesion of heparin to erythrocytes infected by the malaria parasite, Plasmodium falciparum, has been probed by single-molecule force spectroscopy

Not only are parasitized RBCs (pRBCs) more likely to stick to normal red blood cells and to others of their kind, forming clumps known as rosettes, they can also adhere to the walls of capillaries, making them narrower. These are characteristic events in severe malaria and can be fatal. A particular protein expressed on the surface of pRBCs, PfEMP1, is known to be involved in facilitating their attachment to each other and to the capillary walls, so disrupting this protein could help prevent this happening.

“We used heparin, a glycosaminoglycan (GAG, a type of polysaccharide), together with pRBCs as a model to study GAG-pRBC interactions at the individual molecule level for the first time,” says Dr. Xavier Fernàndez-Busquets, a senior researcher in the Nanobioengineering group. “Using fluorescence microscopy, fluorescence-assisted cell sorting, and single-molecule force spectroscopy, we found that heparin binds specifically to infected RBCs, but not to uninfected cells.”

This could allow the development of pRBC-specific antimalarial therapies based on heparin or a similar molecule as targeting element. “It might be a much cheaper approach than the alternative of using antibodies,” says Xavier. “This is particularly important, since malaria is mainly found in the developing world.”

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