title: Annular oligomeric amyloid intermediates observed by in situ atomic force microscopy.
abstract: Amyloidoses and related protein deposition diseases involve the transformation of normally soluble proteins into insoluble deposits, usually fibrillar in nature. Although it was originally assumed that the fibrils were the toxic species, this assumption has recently been called into question. Accumulating evidence in several systems suggests that oligomeric intermediates on the aggregation pathway may be toxic. In the present study we used in situ atomic force microscopy to monitor aggregation in aqueous solution in real time. The sample used was an amyloidogenic immunoglobulin light chain, involved in AL or light chain amyloidosis. The nature of the observed oligomeric intermediates was dependent on the conditions of incubation, especially pH and ionic strength. Several different aggregation intermediates with a variety of morphologies, including annular or torus-shaped species, were observed. The data indicate that protein aggregation can be very complex, involving a variety of different oligomeric intermediates whose population will be determined by the kinetic and thermodynamic competition between them.
authors.affiliation: Department of Chemistry and Biochemistry, University of California, Santa Cruz 95064, USA.
authors.forename: Min
authors.initials: M
authors.lastname: Zhu
authors.forename: Shubo
authors.initials: S
authors.lastname: Han
authors.forename: Feimeng
authors.initials: F
authors.lastname: Zhou
authors.forename: Sue A
authors.initials: SA
authors.lastname: Carter
authors.forename: Anthony L
authors.initials: AL
authors.lastname: Fink
mesh_terms: D000538:Aluminum Silicates / Q000737:chemistry; D000682:Amyloid / Q000737:chemistry*; D052160:Benzothiazoles; D006863:Hydrogen-Ion Concentration; D007477:Ions; D007700:Kinetics; D018625:Microscopy, Atomic Force / Q000379:methods*; D017434:Protein Structure, Tertiary; D012965:Sodium Chloride / Q000494:pharmacology; D013696:Temperature; D013816:Thermodynamics; D013844:Thiazoles / Q000737:chemistry; D013997:Time Factors
chemical_list: D000538:Aluminum Silicates; D000682:Amyloid; D052160:Benzothiazoles; D007477:Ions; D013844:Thiazoles; C009462:thioflavin T; D012965:Sodium Chloride; C011934:mica