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

TY - JOUR

T1 - Scanning tunneling microscopy reveals single-molecule insights into the self-assembly of amyloid fibrils

AU - Kalashnyk, Nataliya

AU - Nielsen, Jakob T

AU - Nielsen, Erik H

AU - Skrydstrup, Troels

AU - Otzen, Daniel

AU - Lægsgaard, Erik

AU - Wang, Chen

AU - Besenbacher, Flemming

AU - Nielsen, Niels Christian

AU - Linderoth, Trolle R

N1 - Copyright 2012 Elsevier B.V., All rights reserved.

PY - 2012

Y1 - 2012

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84865594280&partnerID=8YFLogxK

U2 - 10.1021/nn301708d

DO - 10.1021/nn301708d

M3 - Journal article

C2 - 22779709

SN - 1936-0851

VL - 6

SP - 6882

EP - 6889

JO - A C S Nano

JF - A C S Nano

IS - 8

ER -