Crystallization of synthetic haemozoin (β-haematin) nucleated at the surface of lipid particles

Date
2010
Authors
Hoang A.N.
Ncokazi K.K.
De Villiers K.A.
Wright D.W.
Egan T.J.
Journal Title
Journal ISSN
Volume Title
Publisher
Abstract
The mechanism of formation of haemozoin, a detoxification by-product of several blood-feeding organisms including malaria parasites, has been a subject of debate; however, recent studies suggest that neutral lipids may serve as a catalyst. In this study, a model system consisting of an emulsion of neutral lipid particles was employed to investigate the formation of β-haematin, the synthetic counterpart of haemozoin, at the lipid-water interface. A solution of monoglyceride, either monostearoylglycerol (MSG) or monopalmitoylglycerol (MPG), dissolved in acetone and methanol was introduced to an aqueous surface. Fluorescence, confocal and transmission electron microscopic (TEM) imaging and dynamic light scattering analysis of samples obtained from beneath the surface confirmed the presence of homogeneous lipid particles existing in two major populations: one in the low micrometre size range and the other in the hundred nanometre range. The introduction of haem (Fe(iii)PPIX) to this lipid particle system under biomimetic conditions (37 °C, pH 4.8) produced β-haematin with apparent first-order kinetics and an average half life of 0.5 min. TEM of monoglycerides (MSG or MPG) extruded through a 200 nm filter with haem produced β-haematin crystals aligned and parallel to the lipid-water interface. These TEM data, together with a model system replacing the lipid with an aqueous organic solvent interface using either methyl laurate or docosane demonstrated that the OH and CO groups are apparently necessary for efficient nucleation. This suggests that β-haematin crystallizes via epitaxial nucleation at the lipid-water interface through interaction of Fe(iii)PPIX with the polar head group. Once nucleated, the crystal grows parallel to the interface until growth is terminated by the curvature of the lipid particle. The hydrophobic nature of the mature crystal favours an interior transport resulting in crystals aligned parallel to the lipid-water interface and each other, strikingly similar to that seen in malaria parasites. © The Royal Society of Chemistry 2010.
Description
Keywords
Aqueous surfaces, Co-group, Docosane, Epitaxial nucleation, First order kinetics, Haemozoin, Half lives, Hydrophobic nature, Laurate, Lipid particles, Malaria parasite, Mechanism of formation, Model system, Monoglycerides, Nanometres, Neutral lipid, Polar headgroups, Size ranges, TEM, Transmission electron, Water interface, Acetone, Biomimetics, Crystals, Detoxification, Dissolution, Emulsification, Iron compounds, Light transmission, Methanol, Nucleation, Organic solvents, Particle size analysis, Phase interfaces, dipalmitoylphosphatidylcholine, heme, hemoprotein, hemozoin, lipid, article, chemistry, crystallization, infrared spectrophotometry, kinetics, transmission electron microscopy, X ray diffraction, 1,2-Dipalmitoylphosphatidylcholine, Crystallization, Heme, Hemeproteins, Kinetics, Lipids, Microscopy, Electron, Transmission, Spectrophotometry, Infrared, X-Ray Diffraction
Citation
Dalton Transactions
39
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