A study led by researchers at the Massachusetts Institute of Technology (MIT) has found out why red blood cells start to lose their ability to deform, and squeeze through tiny blood vessels during the first 24 hours of invasion by the malaria-inducing parasite Plasmodium falciparum.
The researchers knocked out the gene for a parasite protein called RESA (ring-infected erythrocyte surface antigen), and found that the protein, transferred from the parasite to the cell's interior molecular network, had caused red blood cells to become less deformable.
"This is the first time a particular protein has been shown to have such a large effect on red blood cell deformability," said Subra Suresh, Ford Professor of Engineering and senior author of the study.
According to the researchers, their findings may lead to the development of treatments that target the parasite protein.
The RESA protein has long been suspected to be involved in the early stages of that process. The parasite produces RESA during the first stage of malaria, and then transports it to the cell surface.
During the study, the researchers cloned the parasite, knocked out the gene that produces RESA, and then measured the red blood cells' deformability with "optical tweezers" that use lasers to stretch cell membranes.
The deformability remained normal in red blood cells infected by parasites without RESA during the first 24 hours of infection, while in parasites where RESA was turned back on after being knocked out, it was affected in a manner as though the protein was never knocked out.
"That the deformability changed several-fold was a big surprise," said Suresh.
Published online in the Proceedings of the National Academy of Sciences, the study also found that RESA has a much greater impact on the deformability of red blood cells at high fever temperatures than in normal body temperature.
The researchers believe that when RESA travels to the cell membrane, it binds to the cell's cytoskeleton--a scaffolding of proteins that lies just inside the cell membrane.
In future studies, the researchers plan to study the effects of proteins produced by the malaria parasite during later stages of infection. They also plan to look at whether the RESA protein plays any role in why another strain of the malaria parasite, Plasmodium vivax, is less lethal than P. falciparum.