Malaria Parasites are Full of Wildly Spinning Iron Crystals. Scientists Finally Know Why.
Malaria Parasites are Full of Wildly Spinning Iron Crystals. Scientists Finally Know Why.
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Manager, Research Communications, 麻豆学生精品版
Email: sophia.friesen@hsc.utah.edu
Every cell of the deadly Plasmodium falciparum parasite, the organism that causes malaria, contains a tiny compartment full of microscopic iron crystals. As long as the parasite is alive, the crystals dance. They spin, jolt, and ricochet in their little bubble like change in an overclocked washing machine, too fast and chaotic to even be tracked by traditional scientific techniques. And when the parasite dies, they stop.
The iron crystals have long been an important target for antimalarial drugs, but their motion has mystified scientists since it was first detected. 鈥淧eople don鈥檛 talk about what they don鈥檛 understand, and because the motion of these crystals is so mysterious and bizarre, it鈥檚 been a blind spot for parasitology for decades,鈥 says associate professor of biochemistry in the Spencer Fox Eccles School of Medicine (SFESOM) at the University of Utah.
Key points:
- The parasite that causes the deadly disease malaria is full of tiny crystals that constantly spin鈥攁 mystery for decades.
- New research found that the crystals are propelled by peroxide breakdown, the same reaction that launches rockets.
- Crystal spin may help parasites survive by 鈥渂urning off鈥 toxic peroxide or helping store toxic iron compounds.
IMPACT: The results could lead to new malaria medicines and inspire better nanorobots.
Now, Sigala鈥檚 research team has finally found what makes the crystals dance: the same chemical reaction that powers spacefaring rockets.
The findings could reveal new targets for malaria treatments and provide new insights for creating nanoscale robots.
Biological rocket fuel
The crystals, which are made of an iron-based compound called heme, move by triggering the breakdown of hydrogen peroxide into water and oxygen, the researchers discovered. The reaction releases energy, giving the crystals the 鈥渒ick鈥 they need to spin into motion.
It鈥檚 a form of propulsion common in aerospace engineering, where peroxide fuel launches satellites into orbit, but previously unknown in biology. 鈥淭his hydrogen peroxide decomposition has been used to power large-scale rockets,鈥 says postdoctoral fellow in biochemistry in the SFESOM. 鈥淏ut I don鈥檛 think it has ever been observed in biological systems.鈥
Hydrogen peroxide is found at high levels inside the microscopic compartment that contains iron crystals, and parasites make the compound as a waste product, so it had stood out to the researchers as a potential chemical fuel that might power the crystals鈥 motion. Indeed, the scientists found that hydrogen peroxide on its own was enough to set purified crystals spinning鈥攏o parasite required.
Conversely, when the researchers raised malaria parasites at unusually low levels of oxygen, which lowers the amount of peroxide parasites produce, the crystals decelerated to about half their normal speed, even though the parasites were otherwise healthy.
Crystal motion may aid parasite survival
The researchers suspect that the frenetic motion of the crystals may be important for malaria parasites to stay alive, and they have a few ideas why. Peroxide itself is extremely toxic to cells. The spinning crystals might be a way for the malaria organism to 鈥渂urn off鈥 excess toxic peroxide before it can cause harmful chemical reactions and damage the parasite.
Sigala adds that the spinning motion might also help the parasite quickly deal with excess heme by keeping crystals from clumping together. Clumped-up crystals would prevent the parasite from storing additional heme as quickly, because they鈥檇 have less available surface to add new heme to. By keeping the crystals in constant motion, the malaria parasite may ensure that it鈥檚 able to sequester additional heme efficiently.
Powering new robots and new drugs
The spinning crystals are the first known example in biology of a self-propelled metallic nanoparticle, the researchers say. But they suspect that this phenomenon is much more widespread.
The new findings could inspire improved designs for microscopic robots, the researchers add.
鈥淣ano-engineered self-propelling particles can be used for a variety of industrial and drug delivery applications, and we think there are potential insights that will come from these results,鈥 Sigala says.
The results could also eventually lead to better antimalarial drugs, the researchers say. 鈥淲e think that the breakdown of hydrogen peroxide likely makes an important contribution to reducing cellular stress,鈥 Sigala says. 鈥淚f there are ways to block the chemistry at the crystal surface, that alone might be sufficient to kill parasites.鈥
Their tiny chemical rockets are wildly different from any known aspect of human biology鈥攁nd that means that they鈥檙e a powerful potential drug target. Drugs that target such a parasite-unique mechanism are much less likely to have dangerous side effects. 鈥淚f we target a drug to an area that鈥檚 very different from human cells, then it鈥檚 probably not going to have extreme side effects,鈥 Hastings explains. 鈥淚f we can define how this parasite is different from our bodies, it gives us access to new directions for medications.鈥
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The results are published in PNAS as 鈥溾
The work was supported by the National Institutes of Health (grant numbers R35GM133764, R21AI185746, R35GM14749, and T32AI055434), the Utah Center for Iron & Heme Disorders (grant number U54DK110858), the Price College of Engineering at the University of Utah, and the 3i Initiative at 麻豆学生精品版. Content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.