Dual Effect of (LK)nL Peptides on the Onset of Insulin Amyloid Fiber Formation at Hydrophobic Surfaces

Chouchane, Karim; Vendrely, Charlotte; Amari, Myriam; Moreaux, Katie; Brückert, Franz; Weidenhaupt, Marianne

doi:10.1021/acs.jpcb.5b07365

Cited by 7 publications

(9 citation statements)

References 22 publications

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“…It reveals that the increased hydrophobicity brought by G33V mutation alters the associations between other residues and also interferes with the MC-MC interaction. Too much hydrophobic interaction is reported to have a negative effect on the protein stability as well as the formation of an aggregative nucleus in peptides-hydrophobic surface system [ 70 ], or to reduce the β-sheet content of fibrils and lead to disordered oligomers in Aβ 16–22 -crowder system [ 71 ]. In a previous REMD simulation study of G33I mutant Aβ 29–42 dimer, the enhanced hydrophobic at G33 was also reported to reduce intermolecular interaction in WT dimer [ 58 ].…”

Section: Resultsmentioning

confidence: 99%

Assemblies of amyloid-β30–36 hexamer and its G33V/L34T mutants by replica-exchange molecular dynamics simulation

et al. 2017

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The aggregation of amyloid-β peptides is associated with the pathogenesis of Alzheimer’s disease, in which the 30–36 fragments play an important part as a fiber-forming hydrophobic region. The fibrillar structure of Aβ30–36 has been detected by means of X-ray diffraction, but its oligomeric structural determination, biophysical characterization, and pathological mechanism remain elusive. In this study, we have investigated the structures of Aβ30–36 hexamer as well as its G33V and L34T mutants in explicit water environment using replica-exchange molecular dynamics (REMD) simulations. Our results show that the wild-type (WT) Aβ30–36 hexamer has a preference to form β-barrel and bilayer β-sheet conformations, while the G33V or L34T mutation disrupts the β-barrel structures: the G33V mutant is homogenized to adopt β-sheet-rich bilayers, and the structures of L34T mutant on the contrary get more diverse. The hydrophobic interaction plays a critical role in the formation and stability of oligomeric assemblies among all the three systems. In addition, the substitution of G33 by V reduces the β-sheet content in the most populated conformations of Aβ30–36 oligomers through a steric effect. The L34T mutation disturbs the interpeptide hydrogen bonding network, and results in the increased coil content and morphological diversity. Our REMD runs provide structural details of WT and G33V/L34T mutant Aβ30–36 oligomers, and molecular insight into the aggregation mechanism, which will be helpful for designing novel inhibitors or amyloid-based materials.

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Section: Resultsmentioning

confidence: 99%

Assemblies of amyloid-β30–36 hexamer and its G33V/L34T mutants by replica-exchange molecular dynamics simulation

et al. 2017

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“…Some studies have gone a step further to investigate mechanisms of LK peptide aggregation 12−14 and complex/film formation at interfaces. 5,15 Surprisingly fewer experimental studies have focused on the kinetic 16 or thermodynamic aspects of LK peptide adsorption. Thermodynamic analyses are important because they can provide key mechanistic insights into protein self-assembly on surfaces and the basis of protein function and stability in general.…”

Section: ■ Introductionmentioning

confidence: 99%

“…A great number of experimental studies employing a wide variety of techniques such as solid-state nuclear magnetic resonance (ssNMR), near-edge X-ray adsorption fine structure (NEXAFS), , sum frequency generation (SFG), − X-ray photoelectron spectroscopy (XPS), and time-of-flight secondary ion mass spectrometry (ToF-SIMS) have been performed on systems of LK peptides adsorbed to solid surfaces, many with SAM surfaces specifically, to determine the interfacial conformations and orientations of the adsorbed peptides. Some studies have gone a step further to investigate mechanisms of LK peptide aggregation − and complex/film formation at interfaces. , Surprisingly fewer experimental studies have focused on the kinetic or thermodynamic aspects of LK peptide adsorption. Thermodynamic analyses are important because they can provide key mechanistic insights into protein self-assembly on surfaces and the basis of protein function and stability in general .…”

Section: Introductionmentioning

confidence: 99%

Strong Electrostatic Interactions Lead to Entropically Favorable Binding of Peptides to Charged Surfaces

Sprenger

Pfaendtner

2016

Langmuir

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Thermodynamic analyses can provide key insights into the origins of protein self-assembly on surfaces, protein function, and protein stability. However, obtaining quantitative measurements of thermodynamic observables from unbiased classical simulations of peptide or protein adsorption is challenging because of sampling limitations brought on by strong biomolecule/surface binding forces as well as time scale limitations. We used the parallel tempering metadynamics in the well-tempered ensemble (PTMetaD-WTE) enhanced sampling method to study the adsorption behavior and thermodynamics of several explicitly solvated model peptide adsorption systems, providing new molecular-level insight into the biomolecule adsorption process. Specifically studied were peptides LKα14 and LKβ15 and trpcage miniprotein adsorbing onto a charged, hydrophilic self-assembled monolayer surface functionalized with a carboxylic acid/carboxylate headgroup and a neutral, hydrophobic methyl-terminated self-assembled monolayer surface. Binding free energies were calculated as a function of temperature for each system and decomposed into their respective energetic and entropic contributions. We investigated how specific interfacial features such as peptide/surface electrostatic interactions and surface-bound ion content affect the thermodynamic landscape of adsorption and lead to differences in surface-bound conformations of the peptides. Results show that upon adsorption to the charged surface, configurational entropy gains of the released solvent molecules dominate the configurational entropy losses of the bound peptide. This behavior leads to an apparent increase in overall system entropy upon binding and therefore to the surprising and seemingly nonphysical result of an apparent increased binding free energy at elevated temperatures. Opposite effects and conclusions are found for the neutral surface. Additional simulations demonstrate that by adjusting the ionic strength of the solution, results that show the expected physical behavior, i.e., peptide binding strength that decreases with increasing temperature or is independent of temperature altogether, can be recovered on the charged surface. On the basis of this analysis, an overall free energy for the entire thermodynamic cycle for peptide adsorption on charged surfaces is constructed and validated with independent simulations.

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“…This lag phase can be dramatically shortened in the presence of substoichiometric amounts of aggregative peptides (LK9) in solution. 119 Figure 4(c) shows that this acceleration goes in pair with the rapid formation of numerous surface-adsorbed nuclei which are absent when peptide [ Fig. 4(a)] or insulin [ Fig.…”

Section: H Atomic Force Microscopymentioning

confidence: 99%

Comment on “Tuning the bioactivity of bone morphogenetic protein-2 with surface immobilization strategies” by Chen et al.

Cavalcanti‐Adam

Migliorini

2019

Acta Biomaterialia

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The control over the adsorption or grafting of biomolecules from a liquid to a solid interface is of fundamental importance in different fields, such as drug delivery, pharmaceutics, diagnostics, and tissue engineering. It is thus important to understand and characterize how biomolecules interact with surfaces and to quantitatively measure parameters such as adsorbed amount, kinetics of adsorption and desorption, conformation of the adsorbed biomolecules, orientation, and aggregation state. A better understanding of these interfacial phenomena will help optimize the engineering of biofunctional surfaces, preserving the activity of biomolecules and avoiding unwanted side effects. The characterization of molecular adsorption on a solid surface requires the use of analytical techniques, which are able to detect very low quantities of material in a liquid environment without modifying the adsorption process during acquisition. In general, the combination of different techniques will give a more complete characterization of the layers adsorbed onto a substrate. In this review, the authors will introduce the context, then the different factors influencing the adsorption of biomolecules, as well as relevant parameters that characterize their adsorption. They review surface-sensitive techniques which are able to describe different properties of proteins and polymeric films on solid two-dimensional materials and compare these techniques in terms of sensitivity, penetration depth, ease of use, and ability to perform "parallel measurements."

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Dual Effect of (LK)nL Peptides on the Onset of Insulin Amyloid Fiber Formation at Hydrophobic Surfaces

Cited by 7 publications

References 22 publications

Assemblies of amyloid-β30–36 hexamer and its G33V/L34T mutants by replica-exchange molecular dynamics simulation

Assemblies of amyloid-β30–36 hexamer and its G33V/L34T mutants by replica-exchange molecular dynamics simulation

Strong Electrostatic Interactions Lead to Entropically Favorable Binding of Peptides to Charged Surfaces

Comment on “Tuning the bioactivity of bone morphogenetic protein-2 with surface immobilization strategies” by Chen et al.

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