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

Nataliya Kalashnyk; Jakob T Nielsen; Erik H Nielsen; Troels Skrydstrup; Daniel Otzen; Erik Lægsgaard; Chen Wang; Flemming Besenbacher; Niels Christian Nielsen; Trolle R Linderoth

doi:10.1021/nn301708d

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

Nataliya Kalashnyk, Jakob T Nielsen, Erik H Nielsen, Troels Skrydstrup, Daniel Otzen, Erik Lægsgaard, Chen Wang, Flemming Besenbacher, Niels Christian Nielsen, Trolle R Linderoth

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

25 Citations (Scopus)

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.

Original language	English
Journal	A C S Nano
Volume	6
Issue	8
Pages (from-to)	6882-6889
Number of pages	8
ISSN	1936-0851
DOIs	https://doi.org/10.1021/nn301708d
Publication status	Published - 2012

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10.1021/nn301708d

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@article{78bbcf83569c43a496a7bcd697fb9b8f,

title = "Scanning tunneling microscopy reveals single-molecule insights into the self-assembly of amyloid fibrils",

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.",

author = "Nataliya Kalashnyk and Nielsen, {Jakob T} and Nielsen, {Erik H} and Troels Skrydstrup and Daniel Otzen and Erik L{\ae}gsgaard and Chen Wang and Flemming Besenbacher and Nielsen, {Niels Christian} and Linderoth, {Trolle R}",

year = "2012",

doi = "10.1021/nn301708d",

language = "English",

volume = "6",

pages = "6882--6889",

journal = "A C S Nano",

issn = "1936-0851",

publisher = "American Chemical Society",

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}

Scanning tunneling microscopy reveals single-molecule insights into the self-assembly of amyloid fibrils. / Kalashnyk, Nataliya; Nielsen, Jakob T; Nielsen, Erik H et al.
In: A C S Nano, Vol. 6, No. 8, 2012, p. 6882-6889.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

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

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.

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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 -

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

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