Detergent-Mediated Formation of β-Hematin: Heme Crystallization Promoted by Detergents Implicates Nanostructure Formation for Use as a Biological Mimic

dc.creatorSandlin, Rebecca D.
dc.creatorFong, Kim Y.
dc.creatorStiebler, Renata
dc.creatorGulka, Christopher P.
dc.creatorNesbitt, Jenny E.
dc.creatorOliveira, Matheus P.
dc.creatorOliveira, Marcus F.
dc.creatorWright, David W.
dc.date2017-02-23T15:25:40Z
dc.date2017-02-23T15:25:40Z
dc.date2016
dc.date.accessioned2023-09-26T22:07:04Z
dc.date.available2023-09-26T22:07:04Z
dc.identifierSANDLIN, Rebecca D. et al. Detergent-Mediated Formation of β‑Hematin: Heme Crystallization Promoted by Detergents Implicates Nanostructure Formation for Use as a Biological Mimic. Cryst. Growth Des., v.16, n.5, p.2542-2551, Apr. 2016.
dc.identifier1528-7483
dc.identifierhttps://www.arca.fiocruz.br/handle/icict/17892
dc.identifier10.1021/acs.cgd.5b01580
dc.identifier1528-7505
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8874972
dc.descriptionHemozoin is a unique biomineral that results from the sequestration of toxic free heme liberated as a consequence of hemoglobin degradation in the malaria parasite. Synthetic neutral lipid droplets (SNLDs) and phospholipids were previously shown to support the rapid formation of β-hematin, abiological hemozoin, under physiologically relevant pH and temperature, though the mechanism by which heme crystallization occurs remains unclear. Detergents are particularly interesting as a template because they are amphiphilic molecules that spontaneously organize into nanostructures and have been previously shown to mediate β-hematin formation. Here, 11 detergents were investigated to elucidate the physicochemical properties that best recapitulate crystal formation in the parasite. A strong correlation between the detergent's molecular structure and the corresponding kinetics of β-hematin formation was observed, where higher molecular weight polar chains promoted faster reactions. The larger hydrophilic chains correlated to the detergent's ability to rapidly sequester heme into the lipophilic core, allowing for crystal nucleation to occur. The data presented here suggest that detergent nanostructures promote β-hematin formation in a similar manner to SNLDs and phospholipids. Through understanding mediator properties that promote optimal crystal formation, we are able to establish an in vitro assay to probe this drug target pathway.
dc.description2030-01-01
dc.formatapplication/pdf
dc.languageeng
dc.publisherAmerican Chemical Society
dc.rightsrestricted access
dc.subjectHeme
dc.subjectHemina
dc.subjectCristalização
dc.subjectDetergentes
dc.subjectMímica biológica
dc.subjectMalaria
dc.subjectβ‑Hematin
dc.subjectHeme Crystallization
dc.subjectDetergents
dc.subjectBiological Mimic
dc.subjectmalaria
dc.titleDetergent-Mediated Formation of β-Hematin: Heme Crystallization Promoted by Detergents Implicates Nanostructure Formation for Use as a Biological Mimic
dc.typeArticle


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