Aligned hemozoin crystals in curved clusters in malarial red blood cells revealed by nanoprobe X-ray Fe fluorescence and diffraction

Sergey Kapishnikov, Trine Berthing, Lars Hviid, Martin Dierolf, Andreas Menzel, Franz Pfeiffer, Jens Als-Nielsen, Leslie Leiserowitz

Research output: Contribution to journalArticlepeer-review

40 Scopus citations


The human malaria parasite Plasmodium falciparum detoxifies the heme byproduct of hemoglobin digestion in infected red blood cells by sequestration into submicron-sized hemozoin crystals. The crystal is composed of heme units interlinked to form cyclic dimers via reciprocal Fe - O (propionate) bonds. Templated hemozoin nucleation was envisaged to explain a classic observation by electron microscopy of a cluster of aligned hemozoin crystals within the parasite digestive vacuole. This dovetails with evidence that acylglycerol lipids are involved in hemozoin nucleation in vivo, and nucleation of β-hematin, the synthetic analogue of hemozoin, was consistently induced at an acylglycerol-water interface via their {100} crystal faces. In order to ascertain the nature of hemozoin nucleation in vivo, we probed the mutual orientations of hemozoin crystals in situ within RBCs using synchrotron-based X-ray nanoprobe Fe fluorescence and diffraction. The X-ray patterns indicated the presence of hemozoin clusters, each comprising several crystals aligned along their needle c axes and exposing {100} side faces to an approximately cylindrical surface, suggestive of nucleation via a common lipid layer. This experimental finding, and the associated nucleation model, are difficult to reconcile with recent reports of hemozoin formation within lipid droplets in the digestive vacuole. The diffraction results are verified by a study of the nucleation process using emerging tools of three-dimensional cellular microscopy, described in the companion paper.

Original languageEnglish
Pages (from-to)11184-11187
Number of pages4
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number28
StatePublished - 10 Jul 2012


  • Crystal nucleation
  • Lipid-induced precipitation
  • Optical birefringence
  • Submicrofocus X-ray fluorescence
  • X-ray diffraction


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