Low Concentrations of Sodium Dodecyl Sulfate Induce the Extension of β₂-Microglobulin-Related Amyloid Fibrils at a Neutral pH

Abstract

In beta(2)-microglobulin-related (Abeta2M) amyloidosis, partial unfolding of beta(2)-microglobulin (beta2-m) is believed to be prerequisite to its assembly into Abeta2M amyloid fibrils in vivo. Although low pH or 2,2,2-trifluoroethanol at a low concentration has been reported to induce partial unfolding of beta2-m and subsequent amyloid fibril formation in vitro, factors that induce them under near physiological conditions have not been determined. Using fluorescence spectroscopy with thioflavin T, circular dichroism spectroscopy, and electron microscopy, we here show that at low concentrations, sodium dodecyl sulfate (SDS) converts natively folded beta2-m monomers into partially folded, alpha-helix-containing conformers. Surprisingly, this results in the extension of Abeta2M amyloid fibrils at neutral pH, which could be explained basically by a first-order kinetic model. At low concentrations, SDS also stabilized the fibrils at neutral pH. These SDS effects were concentration-dependent and maximal at approximately 0.5 mM, around the critical micelle concentration of SDS (0.67 mM). As the concentration of SDS was increased above 1 mM, the alpha-helix content of beta2-m rose to approximately 10%, while the beta-sheet content decreased to approximately 20%, a change paralleled by a complete cessation of fibril extension and the destabilization of the fibrils. Detergents of other classes had no significant effect on the extension of fibrils. These findings are consistent with the hypothesis that in vivo, specific factors (e.g., phospholipids) that affect the conformation and stability of beta2-m and amyloid fibrils will have significant effects on the kinetics of Abeta2M fibril formation.

Ultrasonication-induced Amyloid Fibril Formation of β2-Microglobulin

“…On the other hand, recent findings by Yamamoto et al (14) and Kihara et al (15) suggest that the extensive fibril formation under physiological conditions can be reproduced under certain conditions such as in the presence of 0.5 mM SDS. Here, we examined the effects of ultrasonication on monomeric ␤2-m at pH 7.0 in the presence of 0.5 mM SDS.…”

“…In contrast, the generation of a substantial amount of amyloid fibrils at neutral pH has been difficult (see below). Recently, Yamamoto et al (14) found that low concentrations of SDS, around the critical micelle concentration (0.7 mM), not only stabilize fibrils but also induce extensive growth of ␤2-m amyloid fibrils at neutral pH. Moreover, Kihara et al (15) found that repeated self-seeding at pH 7.0 with fibrils formed at the same pH results in an acceleration of fibril growth, approaching the phenomenon that occurs under physiological conditions.…”

Benzalkonium Chloride Accelerates the Formation of the Amyloid Fibrils of Corneal Dystrophy-associated Peptides

“…ThT Fluorescence Assay-ThT specifically binds to amyloid fibrils and consequently produce enhanced light emission (18,31,32). The formation of amyloid fibrils was monitored with the ThT fluorescence assay using a microplate (Greiner bio-one 96-well microplate 675-074, made of polystyrene) and a microplate reader (MTP-810, Corona Electric Co., Ibaraki, Japan).…”

Role of Glycosaminoglycan Sulfation in the Formation of Immunoglobulin Light Chain Amyloid Oligomers and Fibrils

“…Thioflavin T forms a complex with fibrils, and the fluorescence intensity is proportional to the amount of fibrils that are present when the concentration of ThT is held constant (16). The effects of ThT buffer solutions on LC structure were evaluated by circular dichroism (CD) and confirmed by TEM and AFM (27)(28)(29)(30).…”