Facile disassembly of amyloid fibrils using gemini surfactant micelles.
The accumulation of a peptide of 38-43 amino acids, in the form of fibrillar plaques, was one of the essential reasons for Alzheimer's disease (AD). Discovering an agent that is able to disassemble and clear disease-associated Abeta peptide fibrils from the brains of AD patients would have critical implications not only in understanding the dynamic process of peptide aggregation but also in the development of therapeutic strategies for AD. This study reported a new finding that cationic gemini surfactant C(12)C(6)C(12)Br(2) micelles can effectively disassemble the Abeta(1-40) fibrils in vitro. Systematic comparisons with other surfactants using ThT fluorescence, AFM, and FTIR techniques suggested that the disassembly effectiveness of gemini surfactant micelles arises from their special molecular structure (i.e., positively bicharged head and twin hydrophobic chains). To track the disassembly process, systematic cryoTEM characterization was also done, which suggested a three-stage disassembly process: (i) Spherical micelles are first absorbed onto the Abeta fibrils because of attractive electrostatic interaction. (ii) Elongated fibrils then disintegrate into short pieces and form nanoscopic aggregates via synergistic hydrophobic and electrostatic interactions. (iii) Finally, complete disaggregation of fibrils and dynamic reassembly result in the formation of peptide/surfactant complexes.
Han
Yuchun
Y
Key Laboratory of Colloid and Interface, Gemini.
He
Chengqian
C
Cao
Meiwen
M
Huang
Xu
X
Wang
Yilin
Y
Li
Zhibo
Z
D000327:Adsorption; D000475:Alkenes; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000378:metabolism*; D057927:Hydrophobic and Hydrophilic Interactions; D008823:Micelles; D008958:Models, Molecular; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects; D011487:Protein Conformation; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology*; D055672:Static Electricity; D013501:Surface-Active Agents / Q000494:pharmacology*
D000475:Alkenes; D016229:Amyloid beta-Peptides; D008823:Micelles; D010446:Peptide Fragments; D000644:Quaternary Ammonium Compounds; D013501:Surface-Active Agents; C078592:amyloid beta-protein (1-40); C509664:hexamethylene-1,6-bis(dodecyldimethylammonium bromide)