Scaffolded multimers of hIAPP(20-29) peptide fragments fibrillate faster and lead to different fibrils compared to the free hIAPP(20-29) peptide fragment.
Applying fibril-forming peptides in nanomaterial design is still challenged by the difficulties in understanding and controlling how fibrils form. The present work investigates the influence of motional restriction on peptide fibrillation. We use cyclotriphosphazene and cyclodextrin as templates to make conjugates of the fibril-forming core of human islet amyloid polypeptide. Attachment of the peptide to the templates resulted in multimers containing six peptide fragments at different positions. ThT fluorescence, CD and FTIR spectroscopy, and AFM and TEM imaging reveal that in both conjugates the peptide retained its fibrillating properties and formed fibrils. However, the conjugate fibrils formed more rapidly than the free peptide and were long and thin, as opposed to the thick and twisted morphology of the intact peptide. Thus the motional restrictions introduced by the scaffold modulate the structure of the fibrils but do not impede the actual fibrillation process.
Interdisciplinary Nanoscience Center (iNANO), Aarhus University, Gustav Wieds Vej 14, DK-8000 Aarhus, Denmark; Center for Insoluble Protein Structures (inSPIN), Aarhus University, Gustav Wieds Vej 14, DK-8000 Aarhus, Denmark.
Heidi F
HF
Christoffersen
Interdisciplinary Nanoscience Center (iNANO), Aarhus University, Gustav Wieds Vej 14, DK-8000 Aarhus, Denmark; Center for Insoluble Protein Structures (inSPIN), Aarhus University, Gustav Wieds Vej 14, DK-8000 Aarhus, Denmark.
Maria
M
Andreasen
Interdisciplinary Nanoscience Center (iNANO), Aarhus University, Gustav Wieds Vej 14, DK-8000 Aarhus, Denmark.
Shuai
S
Zhang
Interdisciplinary Nanoscience Center (iNANO), Aarhus University, Gustav Wieds Vej 14, DK-8000 Aarhus, Denmark; Center for Insoluble Protein Structures (inSPIN), Aarhus University, Gustav Wieds Vej 14, DK-8000 Aarhus, Denmark.
Erik Holm
EH
Nielsen
Department of Biomedicine, Aarhus University, Wilhelm Meyers Allé 4, DK-8000 Aarhus, Denmark.
Gunna
G
Christiansen
Interdisciplinary Nanoscience Center (iNANO), Aarhus University, Gustav Wieds Vej 14, DK-8000 Aarhus, Denmark.
Mingdong
M
Dong
Interdisciplinary Nanoscience Center (iNANO), Aarhus University, Gustav Wieds Vej 14, DK-8000 Aarhus, Denmark; Center for Insoluble Protein Structures (inSPIN), Aarhus University, Gustav Wieds Vej 14, DK-8000 Aarhus, Denmark. Electronic address: ts@inano.au.dk.
Troels
T
Skrydstrup
Interdisciplinary Nanoscience Center (iNANO), Aarhus University, Gustav Wieds Vej 14, DK-8000 Aarhus, Denmark; Center for Insoluble Protein Structures (inSPIN), Aarhus University, Gustav Wieds Vej 14, DK-8000 Aarhus, Denmark. Electronic address: dao@inano.au.dk.
Daniel E
DE
Otzen
D058227:Amyloidogenic Proteins / Q000737:chemistry*; D046529:Microscopy, Electron, Transmission; D010446:Peptide Fragments / Q000737:chemistry*
D058227:Amyloidogenic Proteins; D010446:Peptide Fragments
Amyloid fibrils; Fibrillation; Peptide conjugation; Peptide synthesis