title: Hematin loses its membranotropic activity upon oligomerization into malaria pigment.
abstract: Malaria is an infectious disease caused by Plasmodium type parasites transmitted by the bites of infected female anopheles mosquitoes. The malaria parasite multiplies in red blood cells where it degrades hemoglobin. This degradation of hemoglobin proteins releases hematin, an iron-containing porphyrin, which provokes membrane disruption and lysis. The malaria parasite blocks hematin-induced lysis by biocrystallization, a process that converts hematin into insoluble and chemically inert crystals. Hematin molecules are especially prone to self-assembly as dimers, oligomers and aggregates depending on environmental conditions (pH, solvent, temperature, concentration, ionic strength). Considering the different forms of hematin-based assemblies, it is still unclear which are the ones able to interact with membranes. We have prepared hematin under different conditions to form hematin-based assemblies and to measure their ability to interact and to disorganize membranes. Our results show that different forms of hematin molecules are able to penetrate lipid membranes. Interestingly, this membrane activity is spontaneously inhibited at acidic pH and it can be restored under neutral pH. By contrast, the oligomers of β-hematin were found to be completely harmless toward lipid membranes. Finally, the AFM visualization of hematin interaction with supported lipid bilayers showed for the first time its preferential interaction with defaults in membranes, at the boundaries between two distinct lipid phases. The superficial adsorption of aggregates on membranes and the absence of effect due to oligomers were also confirmed with AFM.
authors: Laboratoire d'excellence GR-Ex, Inserm S1134, Université Paris-Diderot, Institut National de la Transfusion Sanguine, 6, rue Alexandre Cabanel, 75739 Paris cedex 15, France.
authors: Slim
authors: S
authors: Azouzi
authors: Sorbonne universités, Université de technologie de Compiègne, CNRS, Laboratoire de BioMécanique et BioIngénierie UMR 7338, Centre de recherche Royallieu, CS 60 319, 60 203 Compiègne cedex, France.
authors: Karim
authors: K
authors: El Kirat
authors: Sorbonne universités, Université de technologie de Compiègne, CNRS, Laboratoire de Génie Enzymatique et Cellulaire FRE 3580, Centre de recherche Royallieu, CS 60 319, 60 203 Compiègne cedex, France. Electronic address: sandrine.morandat@utc.fr.
authors: Sandrine
authors: S
authors: Morandat
mesh_terms: D015060:1,2-Dipalmitoylphosphatidylcholine / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D002417:Cattle; D002462:Cell Membrane / Q000737:chemistry* / Q000378:metabolism; D019281:Dimerization; D004912:Erythrocytes / Q000378:metabolism / Q000469:parasitology; D006418:Heme / Q000737:chemistry / Q000378:metabolism; D006420:Hemeproteins / Q000737:chemistry* / Q000378:metabolism; D006427:Hemin / Q000737:chemistry* / Q000378:metabolism; D006454:Hemoglobins / Q000737:chemistry / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008051:Lipid Bilayers / Q000737:chemistry* / Q000378:metabolism; D018625:Microscopy, Atomic Force; D015394:Molecular Structure; D010713:Phosphatidylcholines / Q000737:chemistry / Q000378:metabolism; D010963:Plasmodium falciparum / Q000502:physiology; D013552:Swine
chemical_list: D006420:Hemeproteins; D006454:Hemoglobins; D008051:Lipid Bilayers; D010713:Phosphatidylcholines; D015060:1,2-Dipalmitoylphosphatidylcholine; C020753:hemozoin; D006418:Heme; D006427:Hemin; C028694:1-palmitoyl-2-oleoylphosphatidylcholine
keywords: Dimer; Hematin; Hemozoin; Lipid membranes; Monomer; Oligomerization