title: Human serum transferrin fibrils: nanomineralisation in bacteria and destruction of red blood cells.
abstract: Fibrils formed by human serum transferrin [(1-3 μM) apo-Tf, partially iron-saturated (Fe0.6 -Tf) and holo-Tf (Fe2 -Tf) forms], from dilute bicarbonate solutions, were deposited on formvar surfaces and studied by electron microscopy. We observed that possible bacterial contamination appears to give rise to long, pea-pod-like (PPL) structures for Fe2 -Tf, attributable to the formation of polyhydroxybutyrate (PHB) storage granules, under the nutrient-limiting conditions used. These PPL structures contained periodic nanomineralisation sites susceptible to uranyl stain. Extended incubation of transferrin solutions (about four days) gave rise to extensive transferrin fibril structures. Optical microscopy and AFM studies showed that red blood cells (RBCs) readily adhere to these fibrils. Moreover, the fibrils appear to penetrate RBC membranes and to induce rapid cell destruction (within about 5 h). It is speculated that in situations in vivo where transferrin fibrils can form, such interactions might have adverse physiological consequences, and further studies could aid the understanding of related pathological events.
authors.affiliation: Department of Chemistry, University of Warwick, Gibbet Hill Road, Coventry CV4 7AL (UK).
authors.forename: Arindam
authors.initials: A
authors.lastname: Mukherjee
authors.forename: Mark A
authors.initials: MA
authors.lastname: Barnett
authors.forename: V
authors.initials: V
authors.lastname: Venkatesh
authors.forename: Sandeep
authors.initials: S
authors.lastname: Verma
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Sadler
mesh_terms: D001059:Apoproteins / Q000737:chemistry* / Q000494:pharmacology / Q000648:ultrastructure; D001419:Bacteria / Q000254:growth & development / Q000378:metabolism*; D001665:Binding Sites; D002448:Cell Adhesion; D004912:Erythrocytes / Q000166:cytology / Q000187:drug effects*; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D046529:Microscopy, Electron, Transmission; D058105:Polymerization; D000091402:Prohibitins; D011485:Protein Binding; D011487:Protein Conformation; D017693:Sodium Bicarbonate; D012996:Solutions; D014168:Transferrin / Q000737:chemistry* / Q000494:pharmacology / Q000648:ultrastructure
chemical_list: D001059:Apoproteins; C000717328:PHB protein, human; D000091402:Prohibitins; D012996:Solutions; D014168:Transferrin; D017693:Sodium Bicarbonate
keywords: atomic force microscopy; fibrillation; nanomineralisation; red blood cells; siderophores; transferrin