Understanding the surface of hemozoin and its synthetic analogue hematin anhydride
Bibliographic record
Abstract
Hemozoin is a biocrystal widely studied due to its relevance as an antimalarial target, potential diagnosis biomarker, and immune modulator during malaria infection. Many investigations are carried out using the crystals isolated from in vitro or in vivo models, or by producing a synthetic analogue called hematin anhydride. Although most of the structural and morphological properties of both hemozoin and hematin anhydride are understood, little is known about their surface. Studying the surface of the crystals is critical for gaining insight into the physical and chemical interactions involved during hemozoin formation, the mechanism of action of current antimalarials, and its role as immune modulator and biomarker for diagnosis. For this reason, this work aimed to develop a critical understanding of some physicochemical properties of the surface of hemozoin and hematin anhydride. In our first study, we investigated the surface of hematin anhydride produced by two different synthesis methods, one in an aqueous medium and another under anhydrous conditions. We demonstrated that the synthesis selected to produce the crystals impacts their surface properties. The products obtained from both syntheses are non-porous and show different values of the specific surface area, elemental composition and amount of water adsorbed on the surface. We also confirmed the presence of carboxylate groups on the surface of all crystals; their amount also differs depending on sample preparations. In our next study, we collected hemozoin from in vitro cultures of Plasmodium falciparum. We cleaned the surface of the crystals from its organic contaminants by two purification procedures, one involving two additional steps than the other. The crystals showed differing surface properties in terms of composition and amount of organic contaminants adsorbed on the crystals surface. We showed that the surface of hemozoin may never be free of contaminants, either because they are part of the crystalline structure of hemozoin or because the cleaning methods introduced them. Additionally, we demonstrated that carboxylate groups play a crucial role in the interaction between hemozoin or hematin anhydride and biomolecules. In our final investigation, we isolated hemozoin from in vitro and in vivo models of Plasmodium to investigate the composition of the organic layer adhered onto the crystals surface. We demonstrated that the elemental composition of the organic layer does not vary among the crystals sources. We reported for the first time the presence or inorganic species of silicon, calcium and phosphorous associated with hemozoin. By assessing the surface speciation and possible origin of these inorganic species, we showed that silicon could be related to an unknown mechanism exploited by the parasite for defense and survival, while calcium and phosphorus may be related to Ca2+-dependent proteins and phosphorylated proteins, respectively. Finally, we proposed that the inorganic elements could be involved in hemozoin biomineralization, may influence the mode of action of some antimalarials and could play a role in the immunomodulatory properties attributed to hemozoin.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".