Structural and morphological characterization of hemozoin produced by Schistosoma mansoni and Rhodnius prolixus

Abstract

Hemozoin (Hz) is a heme crystal produced upon the digestion of hemoglobin (Hb) by blood-feeding organisms as a main mechanism of heme disposal. The structure of Hz consists of heme dimers bound by reciprocal iron-carboxylate interactions and stabilized by hydrogen bonds. We have recently described heme crystals in the blood fluke, Schistosoma mansoni, and in the kissing bug, Rhodnius prolixus. Here, we characterized the structures and morphologies of the heme crystals from those two organisms and compared them to synthetic b-hematin (bH). Synchrotron radiation X-ray powder diffraction showed that all heme crystals share the same unit cell and structure. The heme crystals isolated from S. mansoni and R. prolixus consisted of very regular units assembled in multicrystalline spherical structures exhibiting remarkably distinct surface morphologies compared to bH. In both organisms, Hz formation occurs inside lipid droplet-like particles or in close association to phospholipid membranes. These results show, for the first time, the structural and morphological characterization of natural Hz samples obtained from these two blood-feeding organisms. Moreover, Hz formation occurring in close association to a hydrophobic environment seems to be a common trend for these organisms and may be crucial to produce very regular shaped phases, allowing the formation of multicrystalline assemblies in the guts of S. mansoni and R. prolixus.

Identification of hydroxyeicosatetraenoic acid components of schistosomal hemozoin

“…While PfHz and BH SEM images portray a biomineral of elongated rectangular crystals with well-defined crystal facets, SmHz images depict the characteristic heterogeneous morphology and large size distribution often attributed to the extracellular environment of Hz formation in S. mansoni (Fig. 1B) [11].…”

“…This dark-brown pigment was recently characterized by Oliveira and coworkers as being structurally identical to P. falciparum Hz (PfHz) and its synthetic analogue, β-hematin (BH) [10,11].…”

Biomimetic Approaches to Understanding the Mechanism of Haemozoin Formation

“…It is however pertinent to the question of how the crystal assembles. (Pagola et al, 2000) and haemozoin from Rhodnius prolixus, Schistosoma mansoni (Oliveira et al, 2005) and Plasmodium falciparum (Walczak et al, 2010;Walczak et al, 2011). Using EXAFS, the authors demonstrated that the anhydrides of these two iron porphyrins have similar local order to haemozoin and that this persists in DMSO at least in the case of Fe(III)mesoporphyrin.…”

“…The unit cell dimensions of haemozoin from S. mansoni and R. prolixus were determined in 2005 and structures determined by Rietveld fitting of experimental parameters obtained from the Xray powder diffraction pattern collected with synchrotron radiation (Oliveira et al, 2005). In this study, the atomic coordinates reported for the original -haematin structure were used and only the unit cell and profile parameters were refined.…”

“…Several factors motivated the investigation of its formation at aqueous/organic interfaces. Firstly, it had already been observed in S. mansoni that haemozoin crystals appeared to form at the lipid/water interface of lipid droplets (Oliveira et al, 2005). Secondly, a molecular dynamics study that showed that in vacuum a - dimer of H 2 O-Fe(III)PPIX in which the axial water ligands are directed outwards spontaneously forms a kind of precursor of the -haematin -Pr dimer in which the propionate group of one Fe(III)PPIX is attracted to the iron centre of the other.…”