Contrasting effects of nanoparticle–protein attraction on amyloid aggregation

Radic, Slaven; Davis, Thomas P.; Ke, Pu Chun; Ding, Feng

doi:10.1039/c5ra20182a

Cited by 56 publications

(52 citation statements)

References 78 publications

(108 reference statements)

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“…As a result, the generally nonspecific attraction between IAPP and PHEA led to the accumulation of peptides on PHEA arms, and the increased local peptide concentration accelerated the aggregation of IAPP consistently with a previous coarse-grained computational study. 55 We also examined the secondary structure of IAPPs and their binding with PHEA along the simulation trajectories (e.g., one of the independent simulations shown in Figure S6), where a general trend of correlation between IAPP-PHEA binding and β-sheet formation in IAPP aggregates was evident. Comparison-average secondary structure contents of the last 25 ns between simulations with and without PHEA (Figure S5C and D) suggest that the PHEA binding did not significantly affect the structures of the aggregates other than accelerated IAPP self-association (Figure S4A).…”

Section: Results and Discussionmentioning

confidence: 99%

Star Polymers Reduce Islet Amyloid Polypeptide Toxicity via Accelerated Amyloid Aggregation

Pilkington

Lai

et al. 2017

Biomacromolecules

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Protein aggregation into amyloid fibrils is a ubiquitous phenomenon across the spectrum of neurodegenerative disorders and type 2 diabetes. A common strategy against amyloidogenesis is to minimize the populations of toxic oligomers and protofibrils by inhibiting protein aggregation with small molecules or nanoparticles. However, melanin synthesis in nature is realized by accelerated protein fibrillation to circumvent accumulation of toxic intermediates. Accordingly, we designed and demonstrated the use of star-shaped poly(2-hydroxyethyl acrylate) (PHEA) nanostructures for promoting aggregation while ameliorating the toxicity of human islet amyloid polypeptide (IAPP), the peptide involved in glycemic control and the pathology of type 2 diabetes. The binding of PHEA elevated the β-sheet content in IAPP aggregates while rendering a new morphology of “stelliform” amyloids originating from the polymers. Atomistic molecular dynamics simulations revealed that the PHEA arms served as rodlike scaffolds for IAPP binding and subsequently accelerated IAPP aggregation by increased local peptide concentration. The tertiary structure of the star nanoparticles was found to be essential for driving the specific interactions required to impel the accelerated IAPP aggregation. This study sheds new light on the structure–toxicity relationship of IAPP and points to the potential of exploiting star polymers as a new class of therapeutic agents against amyloidogenesis.

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Section: Results and Discussionmentioning

confidence: 99%

Star Polymers Reduce Islet Amyloid Polypeptide Toxicity via Accelerated Amyloid Aggregation

Pilkington

Lai

et al. 2017

Biomacromolecules

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“…DMD is a unique type of molecular dynamics algorithm with significantly enhanced sampling efficiency, which has been widely used by our group and other in studying protein folding 22 , aggregation 63 , small molecule/nanoparticle peptides interactions 10,64 . In DMD simulations, the inter-atomic interactions have similar components as conventional molecular mechanics force fields, but the potential functions are modeled by discrete step-wise functions mimicking the continuous potential functions.…”

Section: Methodsmentioning

confidence: 99%

Distinct oligomerization and fibrillization dynamics of amyloid core sequences of amyloid-beta and islet amyloid polypeptide

Sun

Wang

et al. 2017

Phys. Chem. Chem. Phys.

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A direct observation of amyloid aggregation from isolated peptides to cross-β fibrils is crucial for understanding the nucleation-dependence process, but the corresponding macroscopic timescales impose a major computational challenge. Using rapid all-atom discrete molecular dynamics simulations, we capture the oligomerization and fibrillization dynamics of the amyloid core sequences of amyloid-β (Aβ) in Alzheimer’s disease and islet amyloid polypeptide (IAPP) in type-2 diabetes, namely Aβ16–22 and IAPP22–28. Both peptides and their mixture spontaneously assemble into cross-β aggregates in silico, but follow distinct pathways. Aβ16–22 is highly aggregation-prone with a funneled free energy basin toward multi-layer β-sheet aggregates. IAPP22–28, on the other hand, features the accumulation of unstructured oligomers before the nucleation of β-sheets and growth into double-layer β-sheet aggregates. In the presence of Aβ16–22, the aggregation of IAPP22–28 is promoted by forming co-aggregated multi-layer β-sheets. Our study offers a detailed molecular insight to the long-postulated oligomerization-nucleation process in the amyloid aggregations.

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“…222 DMD simulations have also been recently applied to study the effect of NPs on protein amyloid aggregation. 126, 221, 227 …”

Section: Focusing On Biocorona – a Perspective From Atomistic Simulatmentioning

confidence: 99%

NanoEHS beyond toxicity – focusing on biocorona

Lin

Mortimer

Chen

et al. 2017

Environ. Sci.: Nano

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The first phase of environmental health and safety of nanomaterials (nanoEHS) studies has been mainly focused on evidence-based investigations that probe the impact of nanoparticles, nanomaterials and nano-enabled products on biological and ecological systems. The integration of multiple disciplines, including colloidal science, nanomaterial science, chemistry, toxicology/immunology and environmental science, is necessary to understand the implications of nanotechnology for both human health and the environment. While strides have been made in connecting the physicochemical properties of nanomaterials with their hazard potential in tiered models, fundamental understanding of nano-biomolecular interactions and their implications for nanoEHS is largely absent from the literature. Research on nano-biomolecular interactions within the context of natural systems not only provides important clues for deciphering nanotoxicity and nanoparticle-induced pathology, but also presents vast new opportunities for screening beneficial material properties and designing greener products from bottom up. This review highlights new opportunities concerning nano-biomolecular interactions beyond the scope of toxicity.

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Contrasting effects of nanoparticle–protein attraction on amyloid aggregation

Cited by 56 publications

References 78 publications

Star Polymers Reduce Islet Amyloid Polypeptide Toxicity via Accelerated Amyloid Aggregation

Star Polymers Reduce Islet Amyloid Polypeptide Toxicity via Accelerated Amyloid Aggregation

Distinct oligomerization and fibrillization dynamics of amyloid core sequences of amyloid-beta and islet amyloid polypeptide

NanoEHS beyond toxicity – focusing on biocorona

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