title: Collagen plays an active role in the aggregation of beta2-microglobulin under physiopathological conditions of dialysis-related amyloidosis.
abstract: Dialysis-related amyloidosis is characterized by the deposition of insoluble fibrils of beta(2)-microglobulin (beta(2)-m) in the musculoskeletal system. Atomic force microscopy inspection of ex vivo amyloid material reveals the presence of bundles of fibrils often associated to collagen fibrils. Aggregation experiments were undertaken in vitro with the aim of reproducing the physiopathological fibrillation process. To this purpose, atomic force microscopy, fluorescence techniques, and NMR were employed. We found that in temperature and pH conditions similar to those occurring in periarticular tissues in the presence of flogistic processes, beta(2)-m fibrillogenesis takes place in the presence of fibrillar collagen, whereas no fibrils are obtained without collagen. Moreover, the morphology of beta(2)-m fibrils obtained in vitro in the presence of collagen is extremely similar to that observed in the ex vivo sample. This result indicates that collagen plays a crucial role in beta(2)-m amyloid deposition under physiopathological conditions and suggests an explanation for the strict specificity of dialysis-related amyloidosis for the tissues of the skeletal system. We hypothesize that positively charged regions along the collagen fiber could play a direct role in beta(2)-m fibrillogenesis. This hypothesis is sustained by aggregation experiments performed by replacing collagen with a poly-L-lysine-coated mica surface. As shown by NMR measurements, no similar process occurs when poly-L-lysine is dissolved in solution with beta(2)-m. Overall, the findings are consistent with the estimates resulting from a simplified collagen model whereby electrostatic effects can lead to high local concentrations of oppositely charged species, such as beta(2)-m, that decay on moving away from the fiber surface.
authors.affiliation: Department of Physics, University of Genoa, Via Dodecaneso 33, I-16146 Genoa, Italy. relini@mail.fisica.unige.it
authors.forename: Annalisa
authors.initials: A
authors.lastname: Relini
authors.forename: Claudio
authors.initials: C
authors.lastname: Canale
authors.forename: Silvia
authors.initials: S
authors.lastname: De Stefano
authors.forename: Ranieri
authors.initials: R
authors.lastname: Rolandi
authors.forename: Sofia
authors.initials: S
authors.lastname: Giorgetti
authors.forename: Monica
authors.initials: M
authors.lastname: Stoppini
authors.forename: Antonio
authors.initials: A
authors.lastname: Rossi
authors.forename: Federico
authors.initials: F
authors.lastname: Fogolari
authors.forename: Alessandra
authors.initials: A
authors.lastname: Corazza
authors.forename: Gennaro
authors.initials: G
authors.lastname: Esposito
authors.forename: Alessandra
authors.initials: A
authors.lastname: Gliozzi
authors.forename: Vittorio
authors.initials: V
authors.lastname: Bellotti
mesh_terms: D000682:Amyloid / Q000737:chemistry; D000686:Amyloidosis / Q000473:pathology*; D052160:Benzothiazoles; D003094:Collagen / Q000737:chemistry*; D003956:Dialysis; D005109:Extracellular Matrix / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D009682:Magnetic Resonance Spectroscopy; D018625:Microscopy, Atomic Force; D008856:Microscopy, Fluorescence; D011107:Polylysine / Q000737:chemistry; D013696:Temperature; D013844:Thiazoles / Q000737:chemistry; D001613:beta 2-Microglobulin / Q000737:chemistry*
chemical_list: D000682:Amyloid; D052160:Benzothiazoles; D013844:Thiazoles; D001613:beta 2-Microglobulin; C009462:thioflavin T; D011107:Polylysine; D003094:Collagen