Phospholipid Membrane-Mediated Hemozoin Formation: The Effects of Physical Properties and Evidence of Membrane Surrounding Hemozoin

Abstract

Phospholipid membranes are thought to be one of the main inducers of hemozoin formation in Plasmodia and other blood-feeding parasites. The “membrane surrounding hemozoin” has been observed in infected cells but has not been observed in in vitro experiments. This study focused on observing the association of phospholipid membranes and synthetic β-hematin, which is chemically identical to hemozoin, and on a further exploration into the mechanism of phospholipid membrane-induced β-hematin formation. Our results showed that β-hematin formation was induced by phospholipids in the fluid phase but not in the gel phase. The ability of phospholipids to induce β-hematin formation was inversely correlated with gel-to-liquid phase transition temperatures, suggesting an essential insertion of heme into the hydrocarbon chains of the phospholipid membrane to form β-hematin. For this study, a cryogenic transmission electron microscope was used to achieve the first direct observation of the formation of a monolayer of phospholipid membrane surrounding β-hematin.

Lipidic Cubic Phases as a Versatile Platform for the Rapid Detection of Biomarkers, Viruses, Bacteria, and Parasites

“…After this had been successfully assessed, we moved forward to naked‐eye detection of malaria infection by using the same portable device introduced in Figure . It has been reported that lipids and other hydrophobic constituents may enhance and stabilize hemozoin crystallization . Enhancement of crystallization was in fact induced by the lipid mesophases, as shown by Figure c, where an intense birefringent signal was visually observed in few microliters of infected blood reconstituted in meso (Figure c, top image) as compared to a control sample of uninfected blood treated in the same way (Figure c, bottom image).…”

Organism-like formation of Schistosoma hemozoin and its function suggest a mechanism for anti-malarial action of artemisinin

“…However, in the mixture of SGHs and erythrocytes, they can be utilized to form new SHGs. Obviously, erythrocytes plus SHGs meet the recognized requirements of hemozoin formation, including the following: (1) lipids 21 , which are likely from the cell membrane 22 ; (2) heme, which come from haemoglobin in erythrocytes; and (3) pre-existing SHGs, which provide seed to initiate the formation of new SHGs 20 . Notably, no enzymes or proteins were added to the culture, suggesting that no proteins or enzymes were necessary during the process, as in malarial hemozoin 20 .…”

High-Throughput Screening and Prediction Model Building for Novel Hemozoin Inhibitors Using Physicochemical Properties

“…The average mass, octanol-water partition coefficient (Log P), distribution coefficient (Log D), bioconcentration factor (BCF), adsorption coefficient (KOC), number of rule-of-five violations, number of hydrogen bond acceptors, number of hydrogen bond donors, freely rotating bonds, polar surface area, index of refraction, molar refractivity, molar volume, polarizability, flash point, boiling point, enthalpy of vaporization, and number of atoms of chemical elements (such as bromine, carbon, chlorine, fluorine, hydrogen, nitrogen, oxygen, and sulfur) of each of the positive hits and a sample of negative compounds were retrieved from ChemSpider (www.chemspider.com), as predicted by Advanced Chemistry Development (ACD/Laboratories) software (46).…”