Highly accelerated self-assembly and fibrillation of prion peptides on solid surfaces.
The conformational change of cellular prion protein (PrP(C)) to its infectious isoform (PrP(Sc)) is a hallmark of prion diseases. We have developed a novel solid surface-based system for efficient prion fibrillation in vitro by immobilizing prion peptides onto a chemically activated solid surface. The self-assembly of prion peptides into fibrils was more highly accelerated on the solid surface than in solution after 72 h of incubation at 37 degrees C. According to our observation using ex situ atomic force microscopy, fibrils were over 200 nm long and 5-8 nm in diameter. Amyloid-like properties of fibrils self-assembled on the solid surface were confirmed by multiple analyses with circular dichroism and amyloid-specific dyes such as Congo red and thioflavin T. The fibril formation of prion peptides was substantially affected by the incubation temperature, and preformed fibrils disassembled after additional heat treatment at 100 Odegrees . The solid surface-based prion fibrillation system developed in the present work may become a useful tool for the in vitro study of prion aggregation. The adoption of this system will allow the efficient investigation of environmental factors and inhibitor screening.
Ku
Sook Hee
SH
Institute for the BioCentury and Department of Materials Science and Engineering, Korea Advanced Institute of Science and Technology, 373-1 Guseong-dong, Yuseong-gu, Daejeon, Republic of Korea.
Park
Chan Beum
CB
D000595:Amino Acid Sequence; D002942:Circular Dichroism; D006801:Humans; D018625:Microscopy, Atomic Force; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry* / Q000648:ultrastructure; D011328:Prions / Q000737:chemistry* / Q000648:ultrastructure; D013696:Temperature
D010446:Peptide Fragments; D011328:Prions