High-Resolution Electron Microscopy Analysis of Malaria Hemozoin Crystals Reveals New Aspects of Crystal Growth and Elemental Composition

To cope up with toxic effects of heme generation during hemoglobin catabolism, malaria parasites immobilize heme molecules in an inert form known as hemozoin crystal. This mechanism is essential for parasite development and represents a physiological step used as a target for many antimalarial drugs. So far, most of the data on hemozoin structure and elemental composition has been obtained through the analysis of beta-hematin, a synthetic analogue of hemozoin whose structure and physical properties have been the subject of many studies. Fundamental questions regarding crystal growth, immunomodulatory effects, and drug inhibition mechanisms, nevertheless, remain unanswered, especially considering crystals obtained from different malaria species. In this work, we used high-resolution electron microscopy approaches to analyze hemozoin crystals isolated from malaria murine models and compared their structure to isolated crystals obtained from the human malaria parasite Plasmodium falciparum. A comparative analysis of the elemental composition of Hz crystals (isolated or in situ) in murine models was also carried out. Results showed that hemozoin crystals in different Plasmodium species presented a rectangular morphology, with significant size differences between murine and human malaria species. A detailed structural and chemical analysis of the surface of the crystals showed growing areas, indicating points where antimalarial drugs may interfere. Elemental analysis showed that crystals obtained from different species are chemically similar, suggesting that they may potentially perform similar immunomodulatory functions.