TY - JOUR
T1 - Rapid growth of acetylated Aβ(16-20) into macroscopic crystals
AU - Bortolini, Christian
AU - Klausen, Lasse Hyldgaard
AU - Hoffmann, Søren Vrønning
AU - Jones, Nykola C.
AU - Saadeh, Daniela
AU - Wang, Zegao
AU - Knowles, Tuomas P.J.
AU - Dong, Mingdong
N1 - Funding Information:
We thank the Lundbeck Foundation (C.B.), the Carlsberg Foundation (L.H.K.), the Danish Research Council (M.D.), Aarhus University Research Foundation AUFF NOVA-project (M.D.), the Newman Foundation (T.P.J.K), the ERC (T.P.J.K), the BBSRC (T.P.J.K) and ISA (C.B.) for the allocation of beam time on the AU−UV beamline on ASTRID2. D.S. was supported by a Leverhulme Trust Research Leadership Award. The research leading to these results has received funding from the European Research Council under the European Union’s Seventh Framework Programme (FP7/ 2007−2013) through the ERC grant PhysProt (Agreement No. 337969) and through the EU H2020 RISE 2016 (MNR4SCell 734174). C.B. thanks Dr Robert Schuhmann for the very fruitful discussion on growth dynamics of compounds presented in this manuscript.
Publisher Copyright:
© Copyright 2018 American Chemical Society.
PY - 2018/6/26
Y1 - 2018/6/26
N2 - Aberrant assembly of the amyloid-β (Aβ) is responsible for the development of Alzheimer's disease, but can also be exploited to obtain highly functional biomaterials. The short Aβ fragment, KLVFF (Aβ16-20), is crucial for Aβ assembly and considered to be an Aβ aggregation inhibitor. Here, we show that acetylation of KLVFF turns it into an extremely fast self-assembling molecule, reaching macroscopic (i.e., mm) size in seconds. We show that KLVFF is metastable and that the self-assembly can be directed toward a crystalline or fibrillar phase simply through chemical modification, via acetylation or amidation of the peptide. Amidated KLVFF can form amyloid fibrils; we observed folding events of such fibrils occurring in as little as 60 ms. The ability of single KLVFF molecules to rapidly assemble as highly ordered macroscopic structures makes it a promising candidate for applications as a rapid-forming templating material.
AB - Aberrant assembly of the amyloid-β (Aβ) is responsible for the development of Alzheimer's disease, but can also be exploited to obtain highly functional biomaterials. The short Aβ fragment, KLVFF (Aβ16-20), is crucial for Aβ assembly and considered to be an Aβ aggregation inhibitor. Here, we show that acetylation of KLVFF turns it into an extremely fast self-assembling molecule, reaching macroscopic (i.e., mm) size in seconds. We show that KLVFF is metastable and that the self-assembly can be directed toward a crystalline or fibrillar phase simply through chemical modification, via acetylation or amidation of the peptide. Amidated KLVFF can form amyloid fibrils; we observed folding events of such fibrils occurring in as little as 60 ms. The ability of single KLVFF molecules to rapidly assemble as highly ordered macroscopic structures makes it a promising candidate for applications as a rapid-forming templating material.
KW - amyloid crystals
KW - atomic force microscopy
KW - biomaterials
KW - circular dichroism
KW - protein misfolding
KW - self-assembly
KW - stopped-flow
UR - http://www.scopus.com/inward/record.url?scp=85047406160&partnerID=8YFLogxK
UR - https://nottingham-repository.worktribe.com/
U2 - 10.1021/acsnano.8b00448
DO - 10.1021/acsnano.8b00448
M3 - Article
C2 - 29771495
AN - SCOPUS:85047406160
SN - 1936-0851
VL - 12
SP - 5408
EP - 5416
JO - ACS Nano
JF - ACS Nano
IS - 6
ER -