Crystallization of Synthetic Hemozoin (Beta-Hematin) Nucleated at the Surface of Synthetic Neutral Lipid Bodies

The mechanism of formation of hemozoin, 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 synthetic lipid bodies, resembling their in vivo counterpart in composition and size, was employed to investigate the formation of β-hematin, synthetic hemozoin, at the lipid-water interface. The introduction of heme (Fe(III)PPIX) to this synthetic neutral lipid bodies system under biomimetic conditions (37°C, pH 4.8) produced beta-hematin with apparent first order kinetics and an average half life of 0.5 min. TEM of monoglycerides (MPG) extruded through a 200 nm filter with heme produced beta-hematin crystals aligned and parallel to the lipid/water interface. TEM data suggests that beta-hematin crystallizes via epitaxial nucleation at the lipid-water interface through interaction of Fe(III)PPIX with the polar head group and elongation occurs parallel this interface.