title: Monitoring the assembly of Ig light-chain amyloid fibrils by atomic force microscopy.
abstract: Aggregation of Ig light chains to form amyloid fibrils is a characteristic feature of light-chain amyloidosis, a light-chain deposition disease. A recombinant variable domain of the light chain SMA was used to form amyloid fibrils in vitro. Fibril formation was monitored by atomic force microscopy imaging. Single filaments 2.4 nm in diameter were predominant at early times; protofibrils 4.0 nm in diameter were predominant at intermediate times; type I and type II fibrils 8.0 nm and 6.0 nm in diameter, respectively, were predominant at the endpoints. The increase in number of fibrils correlated with increased binding of the fluorescent dye thioflavin T. The fibrils and protofibrils showed a braided structure, suggesting that their formation involves the winding of protofibrils and filaments, respectively. These observations support a model in which two filaments combine to form a protofibril, two protofibrils intertwine to form a type I fibril, and three filaments form a type II fibril.
authors.affiliation: Department of Physics, University of California, Santa Cruz, CA 95064, USA.
authors.forename: C
authors.initials: C
authors.lastname: Ionescu-Zanetti
authors.forename: R
authors.initials: R
authors.lastname: Khurana
authors.forename: J R
authors.initials: JR
authors.lastname: Gillespie
authors.forename: J S
authors.initials: JS
authors.lastname: Petrick
authors.forename: L C
authors.initials: LC
authors.lastname: Trabachino
authors.forename: L J
authors.initials: LJ
authors.lastname: Minert
authors.forename: S A
authors.initials: SA
authors.lastname: Carter
authors.forename: A L
authors.initials: AL
authors.lastname: Fink
mesh_terms: D000682:Amyloid / Q000737:chemistry*; D005456:Fluorescent Dyes / Q000737:chemistry; D007147:Immunoglobulin Light Chains / Q000737:chemistry*; D007700:Kinetics; D018625:Microscopy, Atomic Force; D008954:Models, Biological
chemical_list: D000682:Amyloid; D005456:Fluorescent Dyes; D007147:Immunoglobulin Light Chains