Effect of Terminal Modifications on the Adsorption and Assembly of hIAPP(20–29)

Hajiraissi, Roozbeh; Hanke, Marcel; Orive, Alejandro González; Duderija, Belma; U, Hofmann; Zhang, Yixin; Grundmeier, Guido; Keller, Adrian

doi:10.1021/acsomega.8b03028

Cited by 16 publications

(15 citation statements)

References 82 publications

(146 reference statements)

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“…In that case adsorption was driven by electrostatic interactions between the negatively-charged citrate and positively charged lysine residue. Recent work on the hIAPP20-29 fragment with different terminal charges 60 has demonstrated the complex role that electrostatic interactions can play in determine polypeptide structure on surfaces. On the SAMch3 surface hydrophobic residues are, as is intuitively obvious, more likely to be in contact with the surface with the average residue-surface separations for the hydrophobic residues being smaller than for hydrophilic residues (Figure 8(a)).…”

Section: A Surfaces Perturb Protein Structurementioning

confidence: 99%

Effect of surface chemistry on islet amyloid polypeptide conformation

Cheung

2020

Biointerphases

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The formation of dense, linear arrays (fibrils) by biomolecules is the hallmark of a number of degenerative diseases, such as Alzheimer's and type-2 diabetes. Protein fibrils have also attracted interest as building blocks for new materials. It has long been recognised that surfaces can affect the fibrillation process. Recent work on the model fibril forming protein human islet amyloid polypeptide (hIAPP) has shown that while the protein concentration is highest at hydrophobic surfaces, the rate of fibril formation is lower than on other surfaces. To understand this, replica exchange molecular dynamics simulations were used to investigate the conformations that hIAPP adopts on surfaces of different hydrophobicity. The hydrophobic surface stabilizes α-helical structures, which are significantly different to those found on the hydrophilic surface and in bulk solution. There is also a greatly reduced conformational ensemble on the hydrophobic surface, due to long-lived contacts between hydrophobic residues on the protein and the surface. This new microscopic information will help us determine the mechanism of the enhancement of fibril formation on surfaces and provides new insight into the effect of nanointerfaces and protein conformation.Details on simulation convergence and sampling. Analysis of demultiplexed trajectories.Sample simulation input files.

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Section: A Surfaces Perturb Protein Structurementioning

confidence: 99%

Effect of surface chemistry on islet amyloid polypeptide conformation

Cheung

2020

Biointerphases

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“…For each incubation time of 30 and 210 min, two 50-microliter samples were removed from the tube and deposited on two freshly cleaved mica substrates (Ted Pella, Inc., Redding, CA, USA). Mica has an atomically flat surface with a large negative surface charge density [ 94 ] and is, thus, ideally suited for immobilizing the positively charged hIAPP aggregates formed in solution [ 39 , 50 , 55 , 60 ]. After incubation for an additional 15 min, each mica surface was washed with about 4 mL of HPLC-grade water and dried in a stream of ultra-pure air.…”

Section: Methodsmentioning

confidence: 99%

“…While several studies have investigated the influence of surface chemistry and wettability on amyloid aggregation [ 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 ], there are only a few publications so far that have addressed the effect of surface topography [ 23 , 24 , 62 ]. Shezad et al investigated the aggregation of the Alzheimer’s-associated peptide Aβ(1–42) at hydrophobic polystyrene (PS) surfaces with random rough surface topographies [ 23 ].…”

Section: Introductionmentioning

confidence: 99%

Nanoscale Surface Topography Modulates hIAPP Aggregation Pathways at Solid–Liquid Interfaces

Hanke

Yang

et al. 2021

IJMS

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The effects that solid–liquid interfaces exert on the aggregation of proteins and peptides are of high relevance for various fields of basic and applied research, ranging from molecular biology and biomedicine to nanotechnology. While the influence of surface chemistry has received a lot of attention in this context, the role of surface topography has mostly been neglected so far. In this work, therefore, we investigate the aggregation of the type 2 diabetes-associated peptide hormone hIAPP in contact with flat and nanopatterned silicon oxide surfaces. The nanopatterned surfaces are produced by ion beam irradiation, resulting in well-defined anisotropic ripple patterns with heights and periodicities of about 1.5 and 30 nm, respectively. Using time-lapse atomic force microscopy, the morphology of the hIAPP aggregates is characterized quantitatively. Aggregation results in both amorphous aggregates and amyloid fibrils, with the presence of the nanopatterns leading to retarded fibrillization and stronger amorphous aggregation. This is attributed to structural differences in the amorphous aggregates formed at the nanopatterned surface, which result in a lower propensity for nucleating amyloid fibrillization. Our results demonstrate that nanoscale surface topography may modulate peptide and protein aggregation pathways in complex and intricate ways.

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“…This is a consequence of having two charged residues at the end of the peptide; for other cases, where the side chains of the terminal residues are uncharged, changes to the charge states of the termini (e.g. through capping groups) would potentially have a larger effect 82 .…”

Section: B Conformation Of Aβ(16-22) On Metal Surfacesmentioning

confidence: 99%

The amyloidogenic peptide amyloid beta(16-22) displays facet dependent conformation on metal surfaces

Somers

Cheung

2021

Preprint

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Currently, it is not understood how metal nanoparticles influence the formation of protein fibrils, although recent literature highlights that the shape and chemical composition of such nanoparticles can strongly influence the process. Understanding this process at a fundamental level can potentially unlock routes to the development of new therapeutics, as well as novel materials for other applications. This requires a microscopic picture of the behaviour of amyloidogenic proteins on metal surfaces. Using replica exchange molecular dynamics simulations we investigate the adsorption of the model amyloidogenic peptide, Aβ(16-22), on different gold and silver surfaces. While the peptide adsorbs onto these different surfaces, the adsorption can be considered to be enthalphically driven for the gold surfaces and entropically driven for silver. The conformation of the peptide on gold surfaces also shows a strong facet dependence for gold, with fibril-like conformations being promoted in the 100 surface and inhibited on the 111 surface. A smaller degree of facet dependence is seen for silver with the peptide behaving similar on both of these. The difference in the facet dependence can be related to the difference between direct adsorption onto the gold 111 surface, with a preference towards indirect (water mediated) adsorption onto the other surfaces. This new information on the behaviour of an amyloidogenic peptide on metal surfaces can give insight into the size-dependent effect of nanoparticles on fibril formation and the use of surfaces to control fibrillation.

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Effect of Terminal Modifications on the Adsorption and Assembly of hIAPP(20–29)

Cited by 16 publications

References 82 publications

Effect of surface chemistry on islet amyloid polypeptide conformation

Effect of surface chemistry on islet amyloid polypeptide conformation

Nanoscale Surface Topography Modulates hIAPP Aggregation Pathways at Solid–Liquid Interfaces

The amyloidogenic peptide amyloid beta(16-22) displays facet dependent conformation on metal surfaces

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