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ACS Nano. 2012 Aug 28;6(8):6882-9. doi: 10.1021/nn301708d. Epub 2012 Jul 10.

Scanning tunneling microscopy reveals single-molecule insights into the self-assembly of amyloid fibrils.

Author information

1
Sino-Danish Center for Molecular Nanostructures on Surfaces, Interdisciplinary Nanoscience Center (iNANO) and Department of Physics and Astronomy, Aarhus University, DK-8000 Aarhus C, Denmark.

Abstract

Many severe diseases are associated with amyloid fibril deposits in the body caused by protein misfolding. Structural information on amyloid fibrils is accumulating rapidly, but little is known about the assembly of peptides into fibrils at the level of individual molecules. Here we investigate self-assembly of the fibril-forming tetrapeptides KFFE and KVVE on a gold surface under ultraclean vacuum conditions using scanning tunneling microscopy. Combined with restrained molecular dynamics modeling, we identify peptide arrangements with interesting similarities to fibril structures. By resolving individual peptide residues and revealing conformational heterogeneities and dynamics, we demonstrate how conformational correlations may be involved in cooperative fibril growth. Most interestingly, intermolecular interactions prevail over intramolecular interactions, and assembly of the phenyl-rich KFFE peptide appears not to be dominated by π-π interactions. This study offers interesting perspectives for obtaining fundamental single-molecule insights into fibril formation using a surface science approach to study idealized model systems.

PMID:
22779709
DOI:
10.1021/nn301708d
[Indexed for MEDLINE]

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