Effect of Different Salt Ions on the Propensity of Aggregation and on the Structure of Alzheimer’s Aβ(1-40) Amyloid Fibrils

Klement, Karolin; Wieligmann, Karin; Meinhardt, Jessica; Hortschansky, Peter; Richter, Walter; Fändrich, Marcus

doi:10.1016/j.jmb.2007.08.068

Cited by 191 publications

(228 citation statements)

References 56 publications

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“…Indeed, it is difficult to alter the parallel assembly, powered by the stable registration of positive N termini on negative mica surface cavities, for the first layer (25). This also supports previous views (20)(21)(22)32) that peptide self-assembly is strongly influenced by its microenvironment. Even with the same bulk salt solution, parallel assembly was favored for the first layer (due to the attractive interaction with the mica surface), whereas the antiparallel assembly was favored for the second layer.…”

Section: Resultssupporting

confidence: 86%

mentioning

confidence: 99%

“…Salt ions, with their ubiquitous presence in physiological environments, play a critical role in both assembly dynamics and structure (19)(20)(21)(22)(23)(24). In addition to the nonspecific Debye-Hückel screening, specific ionic interactions (i.e., electroselective series) and indirect/direct effects from water structure (i.e., Hofmeister series) have been explored extensively to interpret salt effects (19)(20)(21)(22)(23)(24). For example, the α-syn fibrillization follows the Hofmeister series but not the electroselective series (19), whereas the opposite seems to be true for other proteins, such as glucagon (21), β2-microglobulin (20), and mouse prionic protein (24), indicating the complex nature of the salt effect on molecular assembly.…”

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confidence: 99%

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Salts drive controllable multilayered upright assembly of amyloid-like peptides at mica/water interface

Dai

Kang

Huynh

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Surface-assisted self-assembly of amyloid-like peptides has received considerable interest in both amyloidosis research and nanotechnology in recent years. Despite extensive studies, some controlling factors, such as salts, are still not well understood, even though it is known that some salts can promote peptide selfassemblies through the so-called "salting-out" effect. However, they are usually noncontrollable, disordered, amorphous aggregates. Here, we show via a combined experimental and theoretical approach that a conserved consensus peptide NH 2 -VGGAVVAGV-CONH 2 (GAV-9) (from representative amyloidogenic proteins) can self-assemble into highly ordered, multilayered nanofilaments, with surprising all-upright conformations, under high-salt concentrations. Our atomic force microscopy images also demonstrate that the vertical stacking of multiple layers is highly controllable by tuning the ionic strength, such as from 0 mM (monolayer) to 100 mM (mainly double layer), and to 250 mM MgCl 2 (double, triple, quadruple, and quintuple layers). Our atomistic molecular dynamics simulations then reveal that these individual layers have very different internal nanostructures, with parallel β-sheets in the first monolayer but antiparallel β-sheets in the subsequent upper layers due to their different microenvironment. Further studies show that the growth of multilayered, all-upright nanostructures is a common phenomenon for GAV-9 at the mica/water interface, under a variety of salt types and a wide range of salt concentrations.amyloid peptide | atomic force microscopy | salt effect | self-assembly on mica A better understanding of the self-assembly of highly ordered peptide nanostructures is critical because it not only helps to uncover the pathogenesis of various neurodegenerative diseases (1) but provides an attractive "bottom-up" nanotechnology for de novo nanodevice design (2) and fabrication (3). In addition to a series of factors (4-6) previously discovered to modulate peptide self-assembly, solid substrates have been found to drive this process directly acting as templates (7,8), controlling both assembly kinetics and morphology of amyloid peptide aggregates (8-11). These findings emphasize the importance of the substrate surface, whether it be a cellular membrane or an inorganic solid surface, on the assembly of various peptides, which is critical in many biological processes. It has been shown recently that fibrous nanostructures form a fundamental framework ubiquitous in normal cellular metabolism, including cell division and signaling, as well as in over 27 different human amyloid diseases and 9 in animals (12).Due to the complexity of cellular membranes and associated physiological conditions (13,14), hydrophilic mica and hydrophobic highly oriented pyrolytic graphite (HOPG) are the two commonly used model substrates for the investigation of surface effects (10,11,15). For example, it was found that amyloid-β (Aβ) peptide formed oligomeric protofibrillar aggregates on mica but only 1D nanofilaments on HOPG (...

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Section: Resultssupporting

confidence: 86%

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confidence: 99%

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confidence: 99%

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Salts drive controllable multilayered upright assembly of amyloid-like peptides at mica/water interface

Dai

Kang

Huynh

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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“…Unless indicated otherwise, samples contained 50 μM Aβ(1-40) in 100 μL, 50 mM Hepes buffer, pH 7.4, 20 μM ThT, 10 mM sodium azide with or without 0.1 μg seeds. Instrumental settings were used as described (63).…”

Section: Methodsmentioning

confidence: 99%

Mechanism of amyloid plaque formation suggests an intracellular basis of Aβ pathogenicity

Friedrich

Tepper²,

Rönicke³

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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220

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The formation of extracellular amyloid plaques is a common patho-biochemical event underlying several debilitating human conditions, including Alzheimer’s disease (AD). Considerable evidence implies that AD damage arises primarily from small oligomeric amyloid forms of Aβ peptide, but the precise mechanism of pathogenicity remains to be established. Using a cell culture system that reproducibly leads to the formation of Alzheimer’s Aβ amyloid plaques, we show here that the formation of a single amyloid plaque represents a template-dependent process that critically involves the presence of endocytosis- or phagocytosis-competent cells. Internalized Aβ peptide becomes sorted to multivesicular bodies where fibrils grow out, thus penetrating the vesicular membrane. Upon plaque formation, cells undergo cell death and intracellular amyloid structures become released into the extracellular space. These data imply a mechanism where the pathogenic activity of Aβ is attributed, at least in part, to intracellular aggregates.

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“…Die Eigenschaften der Aminosäure-seitenketten und die chemisch-physikalischen Umgebungsbedingungen beeinflussen jedoch die Wahrscheinlichkeit und Geschwindigkeit der Amyloidbildung [12,16]. Darüber hinaus bestimmen diese Parameter den genauen Bereich der Polypeptidsequenz, die den selbstkomplementären Cross-β-Kern der Amyloidfibrillen ausbildet [24].…”

Section: Biophysikalische Grundlagen Der Amyloidbildungunclassified

Struktur von Amyloidfibrillen

Meinhardt

Fändrich

2009

Pathologe

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Effect of Different Salt Ions on the Propensity of Aggregation and on the Structure of Alzheimer’s Aβ(1-40) Amyloid Fibrils

Cited by 191 publications

References 56 publications

Salts drive controllable multilayered upright assembly of amyloid-like peptides at mica/water interface

Salts drive controllable multilayered upright assembly of amyloid-like peptides at mica/water interface

Mechanism of amyloid plaque formation suggests an intracellular basis of Aβ pathogenicity

Struktur von Amyloidfibrillen

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