Effects of Gold Nanospheres and Nanocubes on Amyloid-Î² Peptide

Subscriber access provided by Iowa State University | Library

Interface Components: Nanoparticles, Colloids, Emulsions, Surfactants, Proteins, Polymers

Effects of Gold Nanospheres and Nanocubes on Amyloid-# Peptide Fibrillation Wentao Wang, Yuchun Han, Yaxun Fan, and Yilin Wang Langmuir, Just Accepted Manuscript • DOI: 10.1021/acs.langmuir.8b04006 • Publication Date (Web): 14 Jan 2019 Downloaded from http://pubs.acs.org on January 18, 2019

Just Accepted “Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted online prior to technical editing, formatting for publication and author proofing. The American Chemical Society provides “Just Accepted” as a service to the research community to expedite the dissemination of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts appear in full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been fully peer reviewed, but should not be considered the official version of record. They are citable by the Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered to authors. Therefore, the “Just Accepted” Web site may not include all articles that will be published in the journal. After a manuscript is technically edited and formatted, it will be removed from the “Just Accepted” Web site and published as an ASAP article. Note that technical editing may introduce minor changes to the manuscript text and/or graphics which could affect content, and all legal disclaimers and ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors or consequences arising from the use of information contained in these “Just Accepted” manuscripts.

is published by the American Chemical Society. 1155 Sixteenth Street N.W., Washington, DC 20036 Published by American Chemical Society. Copyright © American Chemical Society. However, no copyright claim is made to original U.S. Government works, or works produced by employees of any Commonwealth realm Crown government in the course of their duties.

Page 1 of 28 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Langmuir

Effects of Gold Nanospheres and Nanocubes on Amyloid- Peptide Fibrillation

Wentao Wang,†, ‡ Yuchun Han, † Yaxun Fan† and Yilin Wang*† †Key

Laboratory of Colloid, Interface and Chemical Thermodynamics, CAS Research/Education

Center for Excellence in Molecular Sciences, Beijing National Laboratory for Molecular Sciences (BNLMS), Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, People’s Republic of China ‡Department

of Radiochemistry, China Institute of Atomic Energy, Beijing 102413, People’s

Republic of China

ABSTRACT: Direct exposure or intake of engineered nanoparticles (ENPs) to the human body will trigger a series of complicated biological consequences. Especially, ENPs could either up- or down-regulate peptide fibrillation, which is associated with various degenerative diseases like Alzheimer’s and Parkinson’s diseases. This work reports the effects of gold nanoparticles (AuNPs) with different shapes on the aggregation of an amyloid- peptide (A(1-40)) involved in Alzheimer’s disease. Two kinds of AuNPs were investigated, i.e., gold nanospheres (AuNSs, ~20 nm in diameter) and gold nanocubes (AuNCs, ~20 nm in edge length). It was found that AuNPs play a catalytic role in peptide nucleation through interfacial adsorption of A(1-40). AuNSs with hybrid facets have a higher affinity to A(1-40) because of the higher degree of surface atomic unsaturation than that of the {100}-faceted AuNCs. Therefore, AuNSs exert a more significant acceleration effect on the fibrillation process of A(1-40) than AuNCs. Besides, a shape-dependent secondary structure

ACS Paragon Plus Environment

Langmuir 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 2 of 28

transformation of A(1-40) with different AuNPs was observed using a Fourier transform-infrared spectroscopy (FTIR). The variation of peptide-NP and peptide-peptide interaction caused by the shape alteration of AuNPs influences the equilibrium of inter- and intra-molecular hydrogen bonds, which is believed to be responsible for the shape-dependent secondary structure transformation. The study offers a further understanding on the complicated NP-mediated Aβ aggregation, and also facilitates a further development on designing and synthesizing task-specific AuNPs for the amyloid disease diagnosis and therapy. KEYWORDS: gold nanoparticle, shape, amyloid- peptide, fibrillation, secondary structure

INTRODUCTION Nowadays, we are living in an environment wherein accesses to engineered nanoparticles (ENPs) is commonplace.1 ENPs with the size comparable to a virion or bacterium are small enough to penetrate the cellular membrane and accumulate within the cell, and growing evidence has shown that they can enter the human body through skin, food, air, etc.2-5 Once the ENPs enter a biological medium, a myriad of biomolecules, especially proteins and peptides, can immediately interact with the surface of the ENPs due to high surface energy.6 The interaction between biomolecules and ENPs may trigger a series of complicated biological consequences.7-9 In particular, as reported by Linse et al.,10 the presence of the ENPs may cause the proteins/peptides misfolding and aggregation, which may elicit amyloid aggregation related degenerative diseases and neurological disorders including Parkinson's disease (PD), Alzheimer's disease (AD), type 2 diabetes (T2D) and so forth.11-14 Beyond the potential risks, it has been demonstrated that ENPs have a strong capacity to inhibit protein aggregation and thus they could be ideal candidates to combat amyloid diseases.15-18 However, due to


Page 3 of 28 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Langmuir

the complexity of biological systems, possible consequences of the ENPs introduction are still largely unknown, and thorough examination of the biological roles of ENPs, especially the protein-ENPs interaction, is urgently needed. Amyloid-β peptides (Aβ), a class of peptides of 36～43 amino acids generated from specific βand γ-secretase cleavages of amyloid precursor proteins, are the main component of the amyloid plaques found in the brains of AD patients.19 It is generally believed that the formation of Aβ fibrils is the pathologic hallmark of AD and thus inhibition of Aβ fibrillation is a potential therapeutic strategy for the disease.20 Growing evidences show that the oligomers populated during the early aggregation process are more neurotoxicity than mature fibrils.21-23 Recently, ENPs are increasingly recognized as promising candidates for Aβ fibrillation inhibitors due to their inherently valuable properties such as high surface-to-volume ratio and potential ability to cross BBB. Researchers have designed various ENPs (e.g., polymeric NPs, carbon nanotubes, graphene, quantum dots, metal and metal oxide NPs) to inhibit fibrillation or disrupt fibrillar aggregates,24-33 and yet the results suggest that some ENPs actually accelerate fibrillation kinetics, leading to the concerns about the risks of increasing exposure to such ENPs. Therefore, it is of particular importance to further study the effects of the ENPs on Aβ aggregation for the sake of public health security and the safe-design of new-generation nanomedicine. Among these ENPs, gold nanoparticles (AuNPs) are undoubtedly one of the most extensively studied nanomaterials, due to their excellent biocompatibility, intriguing optical properties, and easy fabrication and surface functionalization.34-36 A variety of AuNPs with diverse sizes, shapes and surface properties have been constructed to modulate Aβ fibrillation under intracellular/extracellular spaces.37-44 The results show that AuNPs present the dual effects (i.e., inhibition or acceleration) on


Langmuir 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 4 of 28

Aβ fibrillation depending on their physicochemical properties (e.g., size, shape, charge, surface modification) and concentrations. For example, Gao et al. presented an interesting size effect, i.e., large L-glutathione stabilized AuNPs accelerated Aβ fibrillation, while small AuNPs significantly suppressed the process.45 Up to now, however, most of the researches have focused on the size and surface decoration of AuNPs on the Aβ fibrillation, and the understanding regarding the shape effect is rather limited. Shape, is another kernel parameter of NPs closely relates with the surface area, surface curvature, surface defect and the type of crystallographic plane of NP. In theory, changes in shape can greatly influence the sites and intensities of protein-NP interaction, as well as the spatial arrangement between neighbor proteins, which will actually affect the NPs-mediated fibrillation.39, 46 Recently, Kim, et al.47 found that Aβ could be selectively bound to the long axis of gold nanorods (AuNRs) and fewer fibrils were formed, while fibril networks were generated with gold nanocubes (AuNCs) as all the facets of AuNCs could interact with Aβ. Konar et al.48 reported that star-shaped CuO NPs exhibited a higher inhibiting efficiency on human serum albumin fibrillation than that of rod-, spherical-, and flower-shaped CuO NPs. Similarly, Wang et al.49 illustrated that the fibrillation and conformation transition of islet amyloid polypeptide with AuNPs were lattice plane-dependent. These studies clearly suggest that shape plays an important role in the NP-mediated protein aggregation. However, the interactions between NPs and proteins are typically case-specific, and thus it is a great challenge to illustrate the mechanisms of the shape effect of AuNPs on Aβ aggregation from the understandings about other proteins and NPs. In this work, we have investigated the shape effect of AuNPs on the Aβ(1-40) fibrillation. Two kinds of AuNPs, gold nanospheres (AuNSs, ~20 nm in diameter) and nanocubes (AuNCs, ~20 nm in edge length), were fabricated by a seed-mediated growth, each possessing different surface structures


Page 5 of 28 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Langmuir

but similar surface chemistry. The fibrillation kinetics and the secondary structure variations of the Aβ(1-40) with the two AuNPs were investigated using various microscopic and spectroscopic techniques. We hope that the discussion on AuNPs-mediated Aβ fibrillation would help to further understand NP-protein/peptide interactions at the molecular level and contribute to design safe and effective NPs that interfere with the fibrillation processes. EXPERIMENTAL SECTION Materials. Amyloid- (1-40) (trifluoroacetate salt) (Aβ(1-40), code, 4307-v; lot, 590708) with purity higher than 95% was purchased from Peptide Institute Inc. (Japan). Chloroauric acid (HAuCl4·4H2O) was purchased from Shenyang Jinke Reagents Company. Sodium borohydride (NaBH4), ascorbic acid (AA) and sodium hydroxide (NaOH) of analytical grade were obtained from Beijing

Chemical

Reagents

Plant.

Dimethylsulfoxide

(DMSO)

and

1,1,1,3,3,3-Hexafluoro-2-propanol (HFIP) of analytical grade was purchased from ACROS. Gemini surfactant hexamethylene-1,6-bis(dodecyldimethylammonium bromide) (abbreviated as C12C6C12Br2) was synthesized as reported in literature50 and was used after repeated recrystallization from ethanol. The structure of C12C6C12Br2 was characterized by 1HNMR spectroscopy, mass spectroscopy, and the purity was verified by elemental analysis and surface tension measurements. All of the experiments were carried out in phosphate buffer of pH 7.4 with ionic strength of 10 mM. Pure water was obtained from the Milli-Q equipment. Synthesis and Characterization of AuNPs. Herein, AuNPs were prepared according to a seed-mediated growth method. Gold seeds were synthesized by NaBH4 reduction of HAuCl4 in the presence of gemini surfactant C12C6C12Br2. Briefly, 20 μL of 20 mM HAuCl4 solution was mixed


Langmuir 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 6 of 28

with 2 mL of 10 mM C12C6C12Br2 solution and vortexed, and then 60 μL of 10 mM ice-cold NaBH4 solution was injected quickly into the mixture under vigorous mixing. The seed particles were used within 6-10 h after the preparation. For the preparation of gold nanospheres (AuNSs), the growth solution was prepared as follows: 1 mL of 100 mM C12C6C12Br2 solution, 224 μL of 20 mM HAuCl4 solution and 400 μL of 100 mM NaOH were mixed with 2.86 mL H2O. The pH value of the growth solution was about 11. After that, 140 μL of 50 mM ascorbic acid solution was then added to it and thoroughly mixed. At the meantime, 10 μL of the as-prepared seed solution was added into the growth solution and mixed thoroughly. After the addition of the gold seed solution, the color of the reaction solution changed into wine red, suggesting the formation of larger gold nanospheres. The preparative procedure for the gold nanocubes (AuNCs) was identical with that of AuNSs, except that the amount of NaOH was 200 μL and the corresponding pH value was 6. The as-prepared AuNPs were characterized by transmission electron microscopy (TEM, JEM-1011 100 kV). TEM samples were prepared by placing one drop of the aqueous dispersion of gold product on a carbon-coated copper grid, allowing water to evaporate at ambient temperature. Particle size distributions were estimated from both TEM and SEM images using ImageJ software. At least 300 particles were counted for each kind of nanoparticle to calculate the values of size distribution. The concentration of the AuNPs were measured by UV-Vis Spectra according to Haiss et al.51 Amyloid  (1-40) Preparation. Aβ(1-40) in non-aggregated form was prepared according to a proposed method.52 Briefly, a stock solution was prepared by dissolving 0.52 mg of Aβ(1-40) in 0.60 mL of HFIP, which was incubated at room temperature for ~1 h. Then, the solution was sonicated for 30 min to completely dissolve Aβ(1-40). After that, HFIP was removed by evaporation under a


Page 7 of 28 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Langmuir

gentle stream of nitrogen. Just before the following experiments were initiated, Aβ(1-40) was redissolved in 0.1 mL DMSO and 2.9 mL of phosphate buffer (I = 10 mM, pH = 7.4). Afterwards, the solution was centrifuged at 13000 rpm for 30 min. Finally, the supernatant liquid was withdrawn and kept at 30 °C for the following experiments. The final Aβ(1-40) molar concentration in the stock solution is ∼40 μM. ThT Fluorescence. Fluorescence spectra were collected with a Hitachi F-4500 spectrophotometer. A drop of sample (10 μL) was added into 1 mL of ThT buffer solution (10 μM). A quartz cell with 1 cm path length was used. The fluorescence intensity was measured at an excitation wavelength of 440 nm, and emission spectra were scanned from 460 to 560 nm. The widths of both the excitation slit and the emission slit were set to 5 nm. The fluorescence intensity of solvent blank was subtracted. Atomic Force Microscopy (AFM). AFM observations were carried out with a Multimode Nanoscope IIIa AFM (Digital Instruments, CA). For ambient imaging, 5-10 μL of Aβ(1-40) sample solution was deposited onto a freshly cleaved piece of mica and left to adhere for 5 min. The sample was then briefly rinsed with pure water and dried with a gentle stream of nitrogen. Probes used were etched silicon probes attached to 125 μm cantilevers with nominal spring constant of 40 N/m (Digital Instruments, model RTESPW). All provided morphology images were recorded using a tapping mode at 512 × 512 pixels resolution and a scan speed of 1.0-1.8 Hz. Topographic data were regularly recorded in both trace and retrace to check on scan artifacts. They were shown in the height mode without any image processing except flattening. Analysis of the images was carried out by the Digital Instruments Nanoscope Software (Version 512r2).


Langmuir 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 8 of 28

Fourier Transform-Infrared Spectroscopic (FTIR). Spectra were measured with a Bruker Optics TENSOR-27 FT-IR spectrophotometer. The samples were prepared by vacuum evaporation of a 10 μL drop of sample solution on CaF2 glass slides, followed by buffer exchanging with D2O and dehydration (repeated at least twice). The extracted amide I band contour was subjected to the second derivative calculation and Gaussian curve-fitting analysis. After decomposition of the amide I band (1700-1600 cm-1), the secondary structure contents were estimated using the criteria described by Pelton and Mclean.53

RESULTS AND DISCUSSION Synthesis and Characterization of AuNPs. Since seed-mediated growth strategy was established in the early 2000s by Murphy and El-Sayed groups,54-55 it has rapidly become one of the most popular ways to construct AuNPs with diverse sizes, shapes and architectures. In general, at least one cationic surfactant is needed to direct the seed-mediated growth, wherefore producing positive charged AuNPs decorated with cationic surfactant. It is thereby important to investigate the interaction between cationic surfactant capped AuNPs and protein/peptide to evaluate the potential risks and benefits of these AuNPs. In the present study, two kinds of AuNPs, i.e., AuNSs and AuNCs were synthesized by a cationic gemini surfactant C12C6C12Br2 by adjusting the pH values of the growth solutions with NaOH. The shape and size distribution of the synthesized AuNPs were characterized by SEM, TEM, and UV-Visible spectroscopy. Figure 1a and 1b illustrate the SEM and TEM images of the AuNSs. As can be seen, the NPs are regularly spherical in shape and highly uniform in size. Figure 1c shows the size distribution of the AuNSs, and the calculated average


Page 9 of 28 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Langmuir

diameter is about 19.5 ± 1.6 nm. The optical properties of AuNSs measured by UV-vis spectroscopy depicted in Figure 1d, clearly shows a symmetric surface plasmon absorption at 522 nm, a characteristic feature of the AuNPs.56 As shown in Figure 1e and f, the as-prepared AuNCs are in high quality with 20.7 ± 1.5 nm in average edge length (Figure 1g). The surface plasmon absorption of the AuNCs appears at 530 nm in UV-vis spectrum (Figure 1h), which is accordance with the 20 nm sized AuNCs reported in literature.57 Besides, the surface charge information of the two AuNPs was evaluated by ζ-potential measurement. The ζ-potential values are 39.8 and 41.6 mV for AuNSs and AuNCs respectively (Figure 2), indicating that the two NPs have nearly identical surface charge.

Figure 1. Characterization of the AuNS (a-d) and AuNC (e-h) prepared via a gemini surfactant-assisted seeded growth method. SEM (a) and TEM (b) images, size distribution (c) and SPR spectrum (d) for the AuNS; SEM (e) and TEM (f) images, size distribution (g) and SPR spectrum (h) for the AuNS.


Langmuir 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 10 of 28

Figure 2. Zeta potential distribution of the as-prepared AuNS (a) and AuNC (b). Fibrillation of A with the AuNPs. To demonstrate the effects of the shape of AuNPs on the aggregation behavior of A, 20 M of A was incubated in the absence and presence of 0.1 nM of AuNSs and AuNCs at 30 °C. Thioflavin T (ThT) fluorescence assay was performed to quantify the aggregation process of A(1-40). ThT is a cationic benzothiazole dye. It does not fluoresce in its free state, but can display enhanced fluorescence upon binding to protein/peptide assembly, specifically the binding to the cross β-sheet structure of amyloid aggregates. Moreover, it is proved that the ThT fluorescence intensity is directly related to the amount of amyloid fibrils present in the solution.58 Hence, the ThT fluorescence binding assay has been widely used to detect and quantify the formation of amyloid fibrils. Figure 3 shows the ThT fluorescence spectra of


Page 11 of 28 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Langmuir

A in the absence and presence of AuNPs at different incubation time durations. Figure 4 summarizes the corresponding ThT fluorescence intensity at 486 nm (excit = 440 nm) as a function of time. As shown, the ThT fluorescence intensity of 20 M A(1-40) solution without any AuNPs increases slightly within 72 h, indicating that the content of A(1-40) fibrils is very low. When 0.1 nM AuNSs was introduced, the ThT fluorescence intensity significantly increases with time, which indicates the formation of a great amount of A(1-40) fibrils. Interestingly, further elongation of time will lead to a sharp decrease of ThT fluorescence intensity. The decease of fluorescence intensity does not mean that the content of fibrils reduces, which is attributed to that the fibrils are precipitated to the solution bottom due to the strong fibril aggregation. This will be confirmed by the AFM images shown below. When AuNCs were added into 20 M of A(1-40) solution, the ThT fluorescence intensity is large than that of A(1-40) itself at different measured times, but obviously lower than that with AuNSs. Besides, the variation tendency of the ThT fluorescence intensity in the presence of AuNCs is similar to the case of AuNSs, illustrating that the precipitate also formed in the A(1-40) and AuNCs system. The above results suggest that both AuNS and AuNC can accelerate the fibrillation of A(1-40), but the effect from AuNSs is stronger.


Langmuir

35

1h

A(1-40) A(1-40)&AuNS A(1-40)&AuNC

30 25 20 15 10 5 460

480

500

520

540

40

Fluorescence Intensity


40

35

12 h

A(1-40) A(1-40)&AuNS A(1-40)&AuNC

30 25 20 15 10 5

560

460

480

Wavelength (nm) 35

40

A(1-40) A(1-40)&AuNS A(1-40)&AuNC

24 h

30


40


25 20 15 10 5 460

480

500

520

540

35

500

520

540

560

Wavelength (nm) 48 h

A(1-40) A(1-40)&AuNS A(1-40)&AuNC

30 25 20 15 10 5

560

460

480

Wavelength (nm)

500

520

540

560

Wavelength (nm)

Figure 3. ThT fluorescence emission spectra (excit = 440 nm) of the Aβ(1-40), Aβ(1-40) & AuNS, and Aβ(1-40) & AuNC at different incubation time durations. 8

Relative Intensity

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 12 of 28

A(1-40) A(1-40)&AuNS A(1-40)&AuNC

7 6 5 4 3 2 1 0

10

20

30

40

Time (h)

50

60

70

Figure 4. The ThT fluorescence relative intensity at 486 nm, showing the time dependence of the A(1-40) fibril content of 20 M of A(1-40) solution in the presence and absence of 0.1 nM of AuNS and AuNC. To further investigate the fibrillation processes, time-dependent AFM was performed to monitor the A aggregates at the incubation time durations of 12 h, 24 h, 48 h, and 72 h (Figure 5). For 20


Page 13 of 28 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Langmuir

M A(1-40), no obvious aggregate can be seen at the early stage of 12 h incubation (Figure 5A1), suggesting A(1-40) is still in the form of monomers. At 24 h, small nanoparticles in the height of ~5 nm emerge, attributable to the formation of oligomers (Figure 5A2). Prolonging the incubation time to 48 h leads to an increase in number density of oligomers and the existence of short fibrils (Figure 5A3). When the time was extended to 72 h, obvious fibrils are found as illustrated in Figure 5A4. The fibrillation process agrees well with the typical developing fibrillogenesis process, monomer → oligomer → fibril → amyloid fibrils and plaques.59 Upon the addition of AuNSs, the fibrillation process is dramatically promoted, a lot of short fibrils are found at 12 h incubation, and mature fibrils with several micrometers in length generate after 24 h. Thereafter, the fibrils continue to grow into more and longer mature fibrils which even entangle with each other and form precipitate, in accordance with the ThT fluorescence result. For the A(1-40) sample with AuNCs, although oligomers and short fibrils form at 12 h and continue to grow with time. Interestingly, pudgy fibrils appear rather than the long and thin fibrils after 48 h. Likewise, the pudgy fibrils aggregate in a side-by-side manner to form precipitated aggregates. Clearly, the shape of AuNPs influences not only the fibrillation kinetics of A(1-40) but also the fibril morphologies.


Langmuir 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 14 of 28

Figure 5. AFM images (5 × 5 m2) of the aggregates of A(1-40) (A1-4), A(1-40) & AuNS (B1-4), and A(1-40) & AuNC (C1-4) systems at different incubation time: 12 h (A1, B1, and C1), 24 h (A2, B2, and C2), 48 h (A3, B3, and C3), and 72 h (A4, B4, and C4). Secondary Structures of Aβ(1-40) with AuNPs by FTIR Spectroscopy. FTIR spectroscopy is widely used for characterizing the secondary structure of proteins/peptides, because the amide I band (1700-1600 cm-1, carbonyl stretch of the amides) has been shown to be highly sensitive to the variation of secondary structure of proteins/peptides.60-61 AuNPs used in this study are transparent in the electromagnetic spectrum of 1700-1600 cm-1, so the FTIR measurements of Aβ(1-40) with AuNPs are feasible. Figure 6 shows the FTIR spectra of the Aβ(1-40) fibrils in the absence and presence of AuNPs. These spectra exhibit distinguishable differences, suggesting a shape-dependent structural transition of the Aβ(1-40) fibrils induced by the AuNSs and the AuNCs. In order to obtain


Page 15 of 28 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Langmuir

the structural transition information, the amide I bands were decomposed and the secondary structure contents were estimated (Table 1). Clearly, when AuNSs are introduced, the -helix structure of Aβ(1-40) is greatly reduced to an undetectable level from the FTIR spectrum, while the -sheet and turn structures of the Aβ(1-40) fibrils slightly increase to different extents. As to the A(1-40) fibrils formed with AuNCs, compared with the A(1-40) fibrils incubated without AuNPs, the -helix and turn structures increase and decrease slightly, respectively, but the -sheet content increases only 2.3%, indicating there is no significant effect from the AuNCs on the formation of -sheet structure.

Figure 6. FTIR spectra of the aggregates of Aβ(1–40), Aβ(1–40) & AuNS, and Aβ(1–40) & AuNC.


Langmuir 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 16 of 28

Table 1. The secondary structure contents of the A(1-40) fibrils in A(1-40) itself, A(1-40) & AuNS, and A(1-40) & AuNC derived from the FTIR spectra. Sample

α-Helix (%)

β-Sheet (%)

Turn (%)

Aβ(1–40)

16.4

55.6

28

Aβ(1–40) & AuNS

0

59.2

39.8

Aβ(1–40) & AuNC

22

57.9

20.1

Possible Mechanism of Shape-Dependent AuNP-A Interactions. Peptide fibrillation usually follows a widely accepted nucleation-growth model, wherein the nucleation process represents the rate-determining step in fibrillogenesis.39, 59 The nucleation process is highly dependent on peptide concentration. In a system containing peptide and NPs, being driven by surface energy, the NPs with a huge specific surface area will inevitably adsorb peptide molecules on their surface, leading to a high local concentration of peptide on the nanoparticle surface, which has been shown to be catalysts to promote the nucleation and thus the overall kinetics of the fibrillation.43 The peptide-NP interaction is very complex where the surface property of the used NP plays an important role. Given that crystalline Au is a typical face-centered cubic (fcc) crystal, AuNCs adopt eight {100} facets as their surfaces, while the surface of AuNSs should be bound by hybrid facets. In comparison with AuNCs of flat {100} facets, spherical surface produces a large density of low-coordinated atoms situated on edges and corners of AuNSs.62 Moreover the low-coordinated atoms are much active than the {100} atoms to chemically or physically absorb foreign molecules or ions to minimize the surface energy. This is to say, AuNSs have a stronger interaction with A(1-40) than AuNCs. As a result, AuNSs adsorb a great deal of A(1-40) molecules and quickly reach to the critical concentration for nucleation, showing a noticeable nucleating effect for A(1-40) fibrillation. While AuNCs have a relative weak interaction with A(1-40), thus a longer time is required to achieve the


Page 17 of 28 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Langmuir

nucleation event. The weak nucleating effect results in slow growth kinetics and favors the short but thick fibrils. It is worth noted that the surface of NPs is always covered with the ligand molecules/ions used in synthesis procedures, which should not be ignored when discussing the peptide-NP interactions. Herein, cationic gemini surfactant C12C6C12Br2 was used in the synthesis of AuNPs. Previously, we found low concentration of C12C6C12Br2 can accelerate the nucleation and growth process of A(1-40), so the adsorbed C12C6C12Br2 on AuNPs surface should be concerned.52, 63

Then we used Thermogravimetric analyses (TGA) and  potential measurements to characterize

the surface property of the two kinds of AuNPs. The TGA results show that the concentrations of residual surfactant on the two NPs are very low (10-5~10-6 M) (see the SI), and the  values of the two AuNPs are very close. Therefore, both the contents of residual surfactant and the  values display no obvious differences, indicating the diversity of fibrillation kinetics of A(1-40) is caused by the shape factor of the two AuNPs. That NPs are able to affect peptide self-assembling structure is closely related to the propensity of fibrillization.64 It has been found that β-sheet structures are an ubiquitous trait of amyloid fibrils, where continuous β-sheets are formed with β-strands running perpendicular to the long axis of the fibrils.65 Therefore, if one NP can drive a decrease in α-helical content and promote a significant increase in β-sheets and turns of peptide, it will be considered to have a strong ability to induce the formation of amyloid fibril. As mentioned above, AuNSs greatly suppress the formation of -helix structure while facilitate the -sheet and turn structures of A(1-40), further suggesting that the AuNSs have a strong enhancing effect on fibrillization. However, AuNCs obviously increase the -helix structure and reduce the turn structure of A(1-40), although very slightly promote the formation of the -sheet structure of A(1-40), which corresponds to the observed formation of the


Langmuir 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 18 of 28

short and thick fibrils with a relative low growth kinetics. The variations in conformation transition during the A(1-40) fibrillation with different AuNPs should be affected by the shape difference of the AuNPs. AuNSs favor the crowded arrangement of the A(1-40) molecules on their surfaces because of large unsaturation of the surface atoms, which may shorten the intermolecular distance of the peptides and in turn facilitate the formation of intermolecular hydrogen bonds and bend the molecular skeleton of the A(1-40) molecules. The acceleration in intermolecular hydrogen bonds and suppression in intramolecular hydrogen bonds will restrain the formation of -helix structure but promote the β-sheet structure.60 As a result, AuNSs lead to the β-sheet rich long amyloid fibrils. In contrast, on the surface of AuNCs, because of the lower local concentration of A(1-40), the intermolecular hydrogen bonds may not be favorable in a large scale, and then the intramolecular hydrogen bonds in each A(1-40) molecule are more favorable than the intermolecular hydrogen bonds between the A(1-40) molecules. Thus the content of the -helix structure of A(1-40) is obviously larger in the presence of AuNCs than that in the presence of AuNSs.52,

61

Accordingly

AuNCs only lead to very short amyloid fibrils, although the β-sheet structure still exists in the short fibrils. CONCLUSIONS In summary, by introducing A(1-40) as a model peptide, AuNSs and AuNCs as model NPs, we investigate the influence of NP shape on the peptide fibrillation. The results indicate that the shape of AuNPs affects both the fibrillation kinetics of A(1-40) and the secondary structure of the formed fibrils. The shape-dependent fibrillation of A(1-40) with AuNPs can be interpreted by considering the variations of the peptide-NP interfacial interaction. Compared with AuNCs, AuNSs have a higher unsaturation degree of the surface Au atoms, which makes AuNSs have a higher affinity to


Page 19 of 28 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Langmuir

A(1-40). The stronger NP-peptide interaction results in a more significant accelerating effect on the nucleation and fibrillation of A(1-40). Furthermore, the variation in NP-peptide interaction could greatly influence the superficial density of peptide on NPs, and thereby the mode and strength of the peptide-peptide interaction, which is considered to be a key factor to the shape-dependent secondary structure transformation. Since the physiological function of a peptide is closely related to its aggregate structure, this study suggests that the AuNP shape does influence the aggregation behavior of peptide, and the optimization of such shape parameters will lead to improvements in the design of safe and effective NPs for various biomedical applications. ASSOCIATED CONTENT Supporting Information Thermogravimetric analyses (TGA) of the AuNS and AuNC. The Supporting Information is available free of charge on the ACS Publications website AUTHOR INFORMATION Corresponding Author *E-mail: [email protected] (Y.L.W.). ORCID Yuchun Han: 0000-0002-2928-2633 Yaxun Fan: 0000-0003-0057-0444 Yilin Wang: 0000-0002-8455-390X

Notes The authors declare no competing financial interest. ACKNOWLEDGMENTS


Langmuir 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 20 of 28

We are grateful for financial supports from the National Natural Science Foundation of China (21633002).

REFERENCES (1) Stark, W. J.; Stoessel, P. R.; Wohlleben, W.; Hafner, A. Industrial Applications of Nanoparticles. Chem. Soc. Rev. 2015, 44, 5793-5805. (2) Schaumann, G. E.; Baumann, T.; Lang, F.; Metreveli, G.; Vogel, H.-J. Engineered Nanoparticles in Soils and Waters. Sci. Total. Environ. 2015, 535, 1-2. (3) Schaumann, G. E.; Philippe, A.; Bundschuh, M.; Metreveli, G.; Klitzke, S.; Rakcheev, D.; Grün, A.; Kumahor, S. K.; Kühn, M.; Baumann, T.; Lang, F.; Manz, W.; Schulz, R.; Vogel, H.-J. Understanding the Fate and Biological Effects of Ag- and TiO2-Nanoparticles in the Environment: The Quest for Advanced Analytics and Interdisciplinary Concepts. Sci. Total. Environ. 2015, 535, 3-19. (4) Maynard, A. D.; Aitken, R. J. ‘Safe Handling of Nanotechnology’ Ten Years On. Nat. Nanotechnol. 2016, 11, 998. (5) McClements, D. J.; Xiao, H. Is Nano Safe in Foods? Establishing the Factors Impacting the Gastrointestinal Fate and Toxicity of Organic and Inorganic Food-grade Nanoparticles. npj Science of Food 2017, 1, 6. (6) Cedervall, T.; Lynch, I.; Lindman, S.; Berggård, T.; Thulin, E.; Nilsson, H.; Dawson, K. A.; Linse, S. Understanding the Nanoparticle–Protein Corona Using Methods to Quantify Exchange Rates and Affinities of Proteins for Nanoparticles. Proc. Natl. Acad. Sci. U.S.A. 2007, 104, 2050-2055.


Page 21 of 28 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Langmuir

(7) Carnovale, C.; Bryant, G.; Shukla, R.; Bansal, V. Size, Shape and Surface Chemistry of Nano– Gold Dictate its Cellular Interactions, Uptake and Toxicity. Prog. Mater. Sci. 2016, 83, 152-190. (8) Song, Y.; Li, X.; Du, X. Exposure to Nanoparticles is Related to Pleural Effusion, Pulmonary Fibrosis and Granuloma. Eur. Respir. 2009, 34, 559-567. (9) Wang, Z.; Wang, C.; Liu, S.; He, W.; Wang, L.; Gan, J.; Huang, Z.; Wang, Z.; Wei, H.; Zhang, J.; Dong, L. Specifically Formed Corona on Silica Nanoparticles Enhances Transforming Growth Factor β1 Activity in Triggering Lung Fibrosis. ACS Nano 2017, 11, 1659-1672. (10) Linse, S.; Cabaleiro-Lago, C.; Xue, W.-F.; Lynch, I.; Lindman, S.; Thulin, E.; Radford, S. E.; Dawson, K. A. Nucleation of Protein Fibrillation by Nanoparticles. Proc. Natl. Acad. Sci. U.S.A. 2007, 104, 8691-8696. (11) Selkoe, D. J. Folding Proteins in Fatal Ways. Nature 2003, 426, 900. (12) Aguzzi, A.; O'Connor, T. Protein Aggregation Diseases: Pathogenicity and Therapeutic Perspectives. Nat. Rev. Drug Discov. 2010, 9, 237. (13) DeToma, A. S.; Salamekh, S.; Ramamoorthy, A.; Lim, M. H. Misfolded Proteins in Alzheimer's Disease and Type II Diabetes. Chem. Soc. Rev. 2012, 41, 608-621. (14) Maher, B. A.; Ahmed, I. A. M.; Karloukovski, V.; MacLaren, D. A.; Foulds, P. G.; Allsop, D.; Mann, D. M. A.; Torres-Jardón, R.; Calderon-Garciduenas, L. Magnetite Pollution Nanoparticles in the Human Brain. Proc. Natl. Acad. Sci. U.S.A. 2016, 113, 10797-10801. (15) Leszek, J.; Md Ashraf, G.; Tse, W.; Zhang, J.; Gasiorowski, K.; Avila-Rodriguez, M.; Tarasov, V.; Barreto, G.; Klochkov, S.; Bachurin, S.; Aliev, G. Nanotechnology for Alzheimer Disease. Curr. Alzheimer Res. 2017, 14, 1182-1189. (16) Martín-Rapun, R.; De Matteis, L.; Ambrosone, A.; Garcia-Embid, S.; Gutierrez, L.; M. de la


Langmuir 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 22 of 28

Fuente, J. Targeted Nanoparticles for the Treatment of Alzheimer's Disease. Curr. Pharm. Design 2017, 23, 1927-1952. (17) Brancolini, G.; Maschio, M. C.; Cantarutti, C.; Corazza, A.; Fogolari, F.; Bellotti, V.; Corni, S.; Esposito, G. Citrate Stabilized Gold Nanoparticles Interfere with Amyloid Fibril Formation: D76N and ΔN6 β2-microglobulin Variants. Nanoscale 2018, 10, 4793-4806. (18) Zhang, M.; Mao, X.; Yu, Y.; Wang, C.; Yang, Y.; Wang, C. Nanomaterials for Reducing Amyloid Cytotoxicity. Adv. Mater. 2013, 25, 3780-801. (19) Masters, C. L.; Multhaup, G.; Simms, G.; Pottgiesser, J.; Martins, R. N.; Beyreuther, K. Neuronal Origin of a Cerebral Amyloid: Neurofibrillary Tangles of Alzheimer's Disease Contain the Same Protein as the Amyloid of Plaque Cores and Blood Vessels. EMBO J. 1985, 4, 2757-2763. (20) Murphy, M. P.; LeVine, H. Alzheimer’s Disease and the β-Amyloid Peptide. J Alzheimers Dis. 2010, 19, 311-323. (21) Laganowsky, A.; Liu, C.; Sawaya, M. R.; Whitelegge, J. P.; Park, J.; Zhao, M.; Pensalfini, A.; Soriaga, A. B.; Landau, M.; Teng, P. K.; Cascio, D.; Glabe, C.; David E. Atomic View of a Toxic Amyloid Small Oligomer. Science 2012, 335, 1228-1231. (22) Larson, M. E.; Lesné, S. E. Soluble A Oligomer Production and Toxicity. J. Neurochem. 2012, 120, 125-139. (23) Sun, Y.; Ge, X.; Xing, Y.; Wang, B.; Ding, F. -barrel Oligomers as Common Intermediates of Peptides Self-Assembling into Cross-β Aggregates. Sci. Rep. 2018, 8, 10353. (24) Vácha, R.; Linse, S.; Lund, M. Surface Effects on Aggregation Kinetics of Amyloidogenic Peptides. J. Am. Chem. Soc. 2014, 136, 11776-11782. (25) Cabaleiro-Lago, C.; Quinlan-Pluck, F.; Lynch, I.; Dawson, K. A.; Linse, S. Dual Effect of


Page 23 of 28 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Langmuir

Amino Modified Polystyrene Nanoparticles on Amyloid β Protein Fibrillation. ACS Chem. Neurosci. 2010, 1, 279-287. (26) Xiong, N.; Dong, X.-Y.; Zheng, J.; Liu, F.-F.; Sun, Y. Design of LVFFARK and LVFFARK-Functionalized Nanoparticles for Inhibiting Amyloid β-Protein Fibrillation and Cytotoxicity. ACS Appl. Mater. Interfaces 2015, 7, 5650-5662. (27) Liao, Y.-H.; Chang, Y.-J.; Yoshiike, Y.; Chang, Y.-C.; Chen, Y.-R. Negatively Charged Gold Nanoparticles Inhibit Alzheimer's Amyloid-β Fibrillization, Induce Fibril Dissociation, and Mitigate Neurotoxicity. Small 2012, 8, 3631-3639. (28) Wu, W.-H.; Sun, X.; Yu, Y.-P.; Hu, J.; Zhao, L.; Liu, Q.; Zhao, Y.-F.; Li, Y.-M. TiO2 Nanoparticles Promote β-amyloid Fibrillation in Vitro. Biochem. Bioph. Res. Co. 2008, 373, 315-318. (29) Xiao, L.; Zhao, D.; Chan, W.-H.; Choi, M. M. F.; Li, H.-W. Inhibition of Beta 1–40 Amyloid Fibrillation with N-acetyl-l-cysteine Capped Quantum Dots. Biomaterials 2010, 31, 91-98. (30) Xie, L.; Luo, Y.; Lin, D.; Xi, W.; Yang, X.; Wei, G. The Molecular Mechanism of Fullerene-Inhibited Aggregation of Alzheimer's β-Amyloid Peptide Fragment. Nanoscale 2014, 6, 9752-9762. (31) Kim, D.; Yoo, J. M.; Hwang, H.; Lee, J.; Lee, S. H.; Yun, S. P.; Park, M. J.; Lee, M.; Choi, S.; Kwon, S. H.; Lee, S.; Kwon, S-. H.; Kim, S.; Park, Y. J.; Kinoshita, M.; Lee, Y-. H.; Shin, S.; Paik, S. R.; Lee, S. J.; Lee, S.; Hong B. H.; Ko, H. S. Graphene Quantum Dots Prevent α-Synucleinopathy in Parkinson’s Disease. Nat. Nanotech. 2018, 13, 812-818. (32) Faridi, A.; Sun, Y.; Okazaki, Y.; Peng, G.; Gao, J.; Kakinen, A.; Faridi, P.; Zhao, M.;

Javed,

I.; Purcell, A. W.; Davis, T. P.; Lin, S.; Oda, R.; Ding, F.; Ke, P. C. Mitigating Human IAPP


Langmuir 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 24 of 28

Amyloidogenesis In Vivo with Chiral Silica Nanoribbons. Small, 2018, 14, 1802825. (33) Sun, Y.; Qian, Z.; Wei, G. The Inhibitory Mechanism of A Fullerene Derivative Against Amyloid-β Peptide Aggregation: An Atomistic Simulation Study. Phys. Chem. Chem. Phys. 2016,18, 12582-12591. (34) Yang, X.; Yang, M.; Pang, B.; Vara, M.; Xia, Y. Gold Nanomaterials at Work in Biomedicine. Chem. Rev. 2015, 115, 10410-10488. (35) Shaw, C. F. Gold-Based Therapeutic Agents. Chem. Rev. 1999, 99, 2589-2600. (36) Zhou, W.; Gao, X.; Liu, D.; Chen, X. Gold Nanoparticles for In Vitro Diagnostics. Chem. Rev. 2015, 115, 10575-10636. (37) Anand, B. G.; Dubey, K.; Shekhawat, D. S.; Prajapati, K. P.; Kar, K. Strategically Designed Antifibrotic Gold Nanoparticles to Prevent Collagen Fibril Formation. Langmuir 2017, 33, 13252-13261. (38) Xiong, N.; Zhao, Y.; Dong, X.; Zheng, J.; Sun, Y. Design of a Molecular Hybrid of Dual Peptide Inhibitors Coupled on AuNPs for Enhanced Inhibition of Amyloid β-Protein Aggregation and Cytotoxicity. Small 2017, 13, 1601666. (39) Wang, B.; Pilkington, E. H.; Sun, Y.; Davis, T. P.; Ke, P. C.; Ding, F. Modulating Protein Amyloid Aggregation with Nanomaterials. Environ. Sci.: Nano 2017, 4, 1772-1783. (40) Arimon, M.; Sanz, F.; Giralt, E.; Carulla, N. Template-Assisted Lateral Growth of Amyloid-β42 Fibrils Studied by Differential Labeling with Gold Nanoparticles. Bioconjugate Chem. 2012, 23, 27-32. (41) Olmedo, I.; Araya, E.; Sanz, F.; Medina, E.; Arbiol, J.; Toledo, P.; Álvarez-Lueje, A.; Giralt, E.; Kogan, M. J. How Changes in the Sequence of the Peptide CLPFFD-NH2 Can Modify the


Page 25 of 28 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Langmuir

Conjugation and Stability of Gold Nanoparticles and Their Affinity for β-Amyloid Fibrils. Bioconjugate Chem. 2008, 19, 1154-1163. (42) Lin, D.; He, R.; Li, S.; Xu, Y.; Wang, J.; Wei, G.; Ji, M.; Yang, X. Highly Efficient Destruction of Amyloid-β Fibrils by Femtosecond Laser-Induced Nanoexplosion of Gold Nanorods. ACS Chem. Neurosci. 2016, 7, 1728-1736. (43) Colvin, V. L.; Kulinowski, K. M. Nanoparticles as Catalysts for Protein Fibrillation. Proc. Natl. Acad. Sci. U.S.A. 2007, 104, 8679-8680. (44) Gao, N.; Sun, H.; Dong, K.; Ren, J.; Qu, X. Gold-Nanoparticle-Based Multifunctional Amyloid-β Inhibitor against Alzheimer’s Disease. Chem. Eur. J 2015, 21, 829-835. (45) Gao, G.; Zhang, M.; Gong, D.; Chen, R.; Hu, X.; Sun, T. The Size-effect of Gold Nanoparticles and Nanoclusters in the Inhibition of Amyloid-β Fibrillation. Nanoscale 2017, 9, 4107-4113. (46) Kinnear, C.; Moore, T. L.; Rodriguez-Lorenzo, L.; Rothen-Rutishauser, B.; Petri-Fink, A. Form Follows Function: Nanoparticle Shape and Its Implications for Nanomedicine. Chem. Rev. 2017, 117, 11476-11521. (47) Kim, Y.; Park, J.-H.; Lee, H.; Nam, J.-M. How Do the Size, Charge and Shape of Nanoparticles Affect Amyloid β Aggregation on Brain Lipid Bilayer? Sci. Rep. 2016, 6, 19548. (48) Konar, S.; Sen, S.; Pathak, A. Morphological Effects of CuO Nanostructures on Fibrillation of Human Serum Albumin. J. Phys. Chem. B 2017, 121, 11437-11448. (49) Wang, S.-T.; Lin, Y.; Todorova, N.; Xu, Y.; Mazo, M.; Rana, S.; Leonardo, V.; Amdursky, N.; Spicer, C. D.; Alexander, B. D.; Edwards, A. A.; Matthews, S. J.; Yarovsky, I.; Stevens, M. M. Facet-Dependent Interactions of Islet Amyloid Polypeptide with Gold Nanoparticles: Implications for Fibril Formation and Peptide-Induced Lipid Membrane Disruption. Chem. Mater. 2017, 29,


Langmuir 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 26 of 28

1550-1560. (50) Zana, R.; Talmon, Y. Dependence of Aggregate Morphology on Structure of Dimeric Surfactants. Nature 1993, 362, 228. (51) Haiss, W.; Thanh, N. T. K.; Aveyard, J.; Fernig, D. G. Determination of Size and Concentration of Gold Nanoparticles from UV−Vis Spectra. Anal. Chem. 2007, 79, 4215-4221. (52) Cao, M.; Han, Y.; Wang, J.; Wang, Y. Modulation of Fibrillogenesis of Amyloid β (1−40) Peptide with Cationic Gemini Surfactant. J. Phys. Chem. B 2007, 111, 13436-13443. (53) Pelton, J. T.; McLean, L. R. Spectroscopic Methods for Analysis of Protein Secondary Structure. Anal. Biochem. 2000, 277, 167-176. (54) Lohse, S. E.; Murphy, C. J. The Quest for Shape Control: A History of Gold Nanorod Synthesis. Chem.Mater. 2013, 25, 1250-1261. (55) Nikoobakht, B.; El-Sayed, M. A. Preparation and Growth Mechanism of Gold Nanorods (NRs) Using Seed-Mediated Growth Method. Chem. Mater. 2003, 15, 1957-1962. (56) Bastús, N. G.; Comenge, J.; Puntes, V. Kinetically Controlled Seeded Growth Synthesis of Citrate-Stabilized Gold Nanoparticles of up to 200 nm: Size Focusing versus Ostwald Ripening. Langmuir 2011, 27, 11098-11105. (57) Huang, C.-J.; Chiu, P.-H.; Wang, Y.-H.; Chen, W. R.; Meen, T. H. Synthesis of the Gold Nanocubes by Electrochemical Technique. J. Electrochem. Soc. 2006, 153, D129-D133. (58) Nilsson, M. R. Techniques to Study Amyloid Fibril Formation in Vitro. Methods 2004, 34, 151-160. (59) Mahmoudi, M.; Kalhor, H. R.; Laurent, S.; Lynch, I. Protein Fibrillation and Nanoparticle Interactions: Opportunities and Challenges. Nanoscale 2013, 5, 2570-2588.


Page 27 of 28 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Langmuir

(60) Shaw, C. P.; Middleton, D. A.; Volk, M.; Lévy, R. Amyloid-Derived Peptide Forms Self-Assembled Monolayers on Gold Nanoparticle with a Curvature-Dependent β-Sheet Structure. ACS Nano 2012, 6, 1416-1426. (61) Mandal, H. S.; Kraatz, H.-B. Effect of the Surface Curvature on the Secondary Structure of Peptides Adsorbed on Nanoparticles. J. Am. Chem. Soc. 2007, 129, 6356-6357. (62) Quan, Z.; Wang, Y.; Fang, J. High-Index Faceted Noble Metal Nanocrystals. Acc. Chem. Res. 2013, 46, 191-202. (63) Li, Y.; Cao, M.; Wang, Y. Alzheimer Amyloid β(1−40) Peptide: Interactions with Cationic Gemini and Single-Chain Surfactants. J. Phys. Chem. B 2006, 110, 18040-18045. (64) Szczepankiewicz, O.; Cabaleiro-Lago, C.; Tartaglia, G. G.; Vendruscolo, M.; Hunter, T.; Hunter, G. J.; Nilsson, H.; Thulin, E.; Linse, S. Interactions in the Native State of Monellin, Which Play a Protective Role Against Aggregation. Mol. BioSyst. 2011, 7, 521-532. (65) Pulawski, W.; Ghoshdastider, U.; Andrisano, V.; Filipek, S. Ubiquitous Amyloids. Appl. Biochem. Biotech. 2012, 166, 1626-1643.


Langmuir 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Table of Contents


Page 28 of 28

Effects of Gold Nanospheres and Nanocubes on Amyloid-Î² Peptide

Recommend Documents