Title
Formation of Lamellar Micelle-like Oligomers and Membrane Disruption Revealed by the Study of Short Peptide hIAPP18-27
Author
Ying Wei, Jun Lu, Tong Lu, Feihong Meng, Jia Xu, Li Wang, Yang Li, Liping Wang, Fei Li
Year
2016
Journal
Physical Chemistry Chemical Physics
Abstract
Prefibrillar amyloid aggregates of proteins are known as cytotoxic species and a common pathogenic factor of many degenerative diseases. The mechanism underlying the formation and cytotoxicity of prefibrillar aggregates is believed to be independent of the actual nature of the amyloid protein. In this study, we monitored the formation of the peptide oligomers and examined the disruptive effects of the oligomers on liposomes using human islet amyloid polypeptide fragment hIAPP18-27 as a model peptide. We observed various morphologies of oligomers formed at different aggregation stages precede formation of mature amyloid fibrils. These species of oligomers were sufficiently stable to maintain their structures and properties at an acidic condition. We presented first evidence that a oligomer species with a lamellar crystaline structure and a size of about 20-60 nm in length, 8 nm in width and 1.5 nm in thickness was most disruptive to the membrane containing anionic component and toxic to the INS-1 cells. Our results showed that short peptides, in the light of their slower fibrillation, could be used as a model system in the study of toxic mechanism of misfolding oligomers of amyloid peptides.
Instrument
J-810
Keywords
Circular dichroism, Secondary structure, Vesicle interactions, Biochemistry