title: 3D morphology of the human hepatic ferritin mineral core: new evidence for a subunit structure revealed by single particle analysis of HAADF-STEM images.
abstract: Ferritin, the major iron storage protein, has dual functions; it sequesters redox activity of intracellular iron and facilitates iron turn-over. Here we present high angle annular dark field (HAADF) images from individual hepatic ferritin cores within tissue sections, these images were obtained using spherical aberration corrected scanning transmission electron microscopy (STEM) under controlled electron fluence. HAADF images of the cores suggest a cubic morphology and a polycrystalline (ferrihydrite) subunit structure that is not evident in equivalent bright field images. By calibrating contrast levels in the HAADF images using quantitative electron energy loss spectroscopy, we have estimated the absolute iron content in any one core, and produced a three dimensional reconstruction of the average core morphology. The core is composed of up to eight subunits, consistent with the eight channels in the protein shell that deliver iron to the central cavity. We find no evidence of a crystallographic orientation relationship between core subunits. Our results confirm that the ferritin protein shell acts as a template for core morphology and within the core, small (approximately 2 nm), surface-disordered ferrihydrite subunits connect to leave a low density centre and a high surface area that would allow rapid turn-over of iron in biological systems.
authors.affiliation: Institute for Materials Research, University of Leeds, Leeds LS29JT, UK.
authors.forename: Ying-Hsi
authors.initials: YH
authors.lastname: Pan
authors.forename: Kasim
authors.initials: K
authors.lastname: Sader
authors.forename: Jonathan J
authors.initials: JJ
authors.lastname: Powell
authors.forename: Andrew
authors.initials: A
authors.lastname: Bleloch
authors.forename: Mhairi
authors.initials: M
authors.lastname: Gass
authors.forename: John
authors.initials: J
authors.lastname: Trinick
authors.forename: Alice
authors.initials: A
authors.lastname: Warley
authors.forename: Andy
authors.initials: A
authors.lastname: Li
authors.forename: Rik
authors.initials: R
authors.lastname: Brydson
authors.forename: Andy
authors.initials: A
authors.lastname: Brown
mesh_terms: D001706:Biopsy; D005290:Ferric Compounds / Q000737:chemistry*; D005293:Ferritins / Q000737:chemistry / Q000648:ultrastructure*; D006432:Hemochromatosis / Q000473:pathology; D006485:Hemosiderin / Q000737:chemistry / Q000648:ultrastructure; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods*; D008099:Liver / Q000737:chemistry / Q000473:pathology / Q000648:ultrastructure*; D008855:Microscopy, Electron, Scanning / Q000379:methods*; D008958:Models, Molecular
chemical_list: D005290:Ferric Compounds; C092844:ferric oxyhydroxide; D005293:Ferritins; D006485:Hemosiderin