Amyloid Self‐Assembly of hIAPP8‐20 via the Accumulation of Helical Oligomers, α‐Helix to β‐Sheet Transition,and Formation of β‐Barrel Intermediates

The self‐assembly of human islet amyloid polypeptide (hIAPP) into β‐sheet‐rich nanofibrils is associated with the pathogeny of type 2 diabetes. Soluble hIAPP is intrinsically disordered with N‐terminal residues 8–17 as α‐helices. To understand the contribution of the N‐terminal helix to the aggregation of full‐length hIAPP, here the oligomerization dynamics of the hIAPP fragment 8–20 (hIAPP8‐20) are investigated with combined computational and experimental approaches. hIAPP8‐20 forms cross‐β nanofibrils in silico from isolated helical monomers via the helical oligomers and α‐helices to β‐sheets transition, as confirmed by transmission electron microscopy, atomic force microscopy, circular dichroism spectroscopy, Fourier transform infrared spectroscopy, and reversed‐phase high performance liquid chromatography. The computational results also suggest that the critical nucleus of aggregation corresponds to hexamers, consistent with a recent mass‐spectroscopy study of hIAPP8‐20 aggregation. hIAPP8‐20 oligomers smaller than hexamers are helical and unstable, while the α‐to‐β transition starts from the hexamers. Converted β‐sheet‐rich oligomers first form β‐barrel structures as intermediates before aggregating into cross‐β nanofibrils. This study uncovers a complete picture of hIAPP8‐20 peptide oligomerization, aggregation nucleation via conformational conversion, formation of β‐barrel intermediates, and assembly of cross‐β protofibrils, thereby shedding light on the aggregation of full‐length hIAPP, a hallmark of pancreatic beta‐cell degeneration.     

Carbon Nanodot‐Sensitized Modulation of Alzheimer's β‐Amyloid Self‐Assembly,Disassembly, and Toxicity

The self‐assembly of amyloidogenic peptides into β‐sheet‐rich aggregates is a general feature of many neurodegenerative diseases, including Alzheimer's disease, which signifies the need for the effective attenuation of amyloid aggregation toward alleviating amyloid‐associated neurotoxicity. This study reports that photoluminescent carbon nanodots (CDs) can effectively suppress Alzheimer's β‐amyloid (Aβ) self‐assembly and function as a β‐sheet breaker disintegrating preformed Aβ aggregates. This study synthesizes CDs using ammonium citrate through one‐pot hydrothermal treatment and passivates their surface with branched polyethylenimine (bPEI). The bPEI‐coated CDs (bPEI@CDs) exhibit hydrophilic and cationic surface characteristics, which interact with the negatively charged residues of Aβ peptides, suppressing the aggregation of Aβ peptides. Under light illumination, bPEI@CDs display a more pronounced effect on Aβ aggregation and on the dissociation of β‐sheet‐rich assemblies through the generation of reactive oxygen species from photoactivated bPEI@CDs. The light‐triggered attenuation effect of Aβ aggregation using a series of experiments, including photochemical and microscopic analysis, is verified. Furthermore, the cell viability test confirms the ability of photoactivated bPEI@CDs for the suppression of Aβ‐mediated cytotoxicity, indicating bPEI@CDs' potency as an effective anti‐Aβ neurotoxin agent.     

Guiding the Morphology of Amyloid Assemblies by Electrostatic Capping: from Polymorphic Twisted Fibrils to Uniform Nanorods

Peptides that self‐assemble into cross‐β‐sheet amyloid structures constitute promising building blocks to construct highly ordered proteinaceous materials and nanoparticles. Nevertheless, the intrinsic polymorphism of amyloids and the difficulty of controlling self‐assembly currently limit their usage. In this study, the effect of electrostatic interactions on the supramolecular organization of peptide assemblies is investigated to gain insights into the structural basis of the morphological diversities of amyloids. Different charged capping units are introduced at the N‐terminus of a potent β‐sheet‐forming sequence derived from the 20–29 segment of islet amyloid polypeptide, known to self‐assemble into polymorphic fibrils. By tuning the charge and the electrostatic strength, different mesoscopic morphologies are obtained, including nanorods, rope‐like fibrils, and twisted ribbons. Particularly, the addition of positive capping units leads to the formation of uniform rod‐like assemblies, with lengths that can be modulated by the charge number. It is proposed that electrostatic repulsions between N‐terminal positive charges hinder β‐sheet tape twisting, leading to a unique control over the size of these cytocompatible nanorods by protofilament growth frustration. This study reveals the high susceptibility of amyloid formation to subtle chemical modifications and opens to promising strategies to control the final architecture of proteinaceous assemblies from the peptide sequence.     

Bioinspired Stable and Photoluminescent Assemblies for Power Generation

Peptide assemblies are ideal components for eco‐friendly optoelectronic energy harvesting devices due to their intrinsic biocompatibility, ease of fabrication, and flexible functionalization. However, to date, their practical applications have been limited due to the difficulty in obtaining stable, high‐performance devices. Here, it is shown that the tryptophan‐based simplest peptide cyclo‐glycine‐tryptophan (cyclo‐GW) forms mechanically robust (elastic modulus up to 24.0 GPa) and thermally stable up to 370 °C monoclinic crystals, due to a supramolecular packing combining dense parallel β‐sheet hydrogen bonding and herringbone edge‐to‐face aromatic interactions. The directional and extensive driving forces further confer unique optical properties, including aggregation‐induced blue emission and unusual stable photoluminescence. Moreover, the crystals produce a high and sustained open‐circuit voltage (1.2 V) due to a high piezoelectric coefficient of 14.1 pC N^?1. These findings demonstrate the feasibility of utilizing self‐assembling peptides for fabrication of biointegrated microdevices that combine high structural stability, tailored optoelectronics, and significant energy harvesting properties.     

Nanoscale Heterogeneity of the Molecular Structure of Individual hIAPP Amyloid Fibrils Revealed with Tip‐Enhanced Raman Spectroscopy

Type 2 diabetes mellitus is characterized by the pathological deposition of fibrillized protein, known as amyloids. It is thought that oligomers and/or amyloid fibrils formed from human islet amyloid polypeptide (hIAPP or amylin) cause cell death by membrane damage. The molecular structure of hIAPP amyloid fibrils is dominated by β‐sheet structure, as probed with conventional infrared and Raman vibrational spectroscopy. However, with these techniques it is not possible to distinguish between the core and the surface structure of the fibrils. Since the fibril surface crucially affects amyloid toxicity, it is essential to know its structure. Here the surface molecular structure and amino acid residue composition of hIAPP fibrils are specifically probed with nanoscale resolution using tip‐enhanced Raman spectroscopy (TERS). The fibril surface mainly contains unordered or α‐helical structures, in contrast to the β‐sheet‐rich core. This experimentally validates recent models of hIAPP amyloids based on NMR measurements. Spatial mapping of the surface structure reveals a highly heterogeneous surface structure. Finally, TERS can probe fibrils formed on a lipid interface, which is more representative of amyloids in vivo.     

Beta‐Sheet‐Forming,Self‐Assembled Peptide Nanomaterials towards Optical,Energy, and Healthcare Applications

Peptide self‐assembly is an attractive route for the synthesis of intricate organic nanostructures that possess remarkable structural variety and biocompatibility. Recent studies on peptide‐based, self‐assembled materials have expanded beyond the construction of high‐order architectures; they are now reporting new functional materials that have application in the emerging fields such as artificial photosynthesis and rechargeable batteries. Nevertheless, there have been few reviews particularly concentrating on such versatile, emerging applications. Herein, recent advances in the synthesis of self‐assembled peptide nanomaterials (e.g., cross β‐sheet‐based amyloid nanostructures, peptide amphiphiles) are selectively reviewed and their new applications in diverse, interdisciplinary fields are described, ranging from optics and energy storage/conversion to healthcare. The applications of peptide‐based self‐assembled materials in unconventional fields are also highlighted, such as photoluminescent peptide nanostructures, artificial photosynthetic peptide nanomaterials, and lithium‐ion battery components. The relation of such functional materials to the rapidly progressing biomedical applications of peptide self‐assembly, which include biosensors/chips and regenerative medicine, are discussed. The combination of strategies shown in these applications would further promote the discovery of novel, functional, small materials.     

Nanoparticle‐Induced Folding and Fibril Formation of Coiled‐Coil‐Based Model Peptides

Nanomedicine is a rapidly growing field that has the potential to deliver treatments for many illnesses. However, relatively little is known about the biological risks of nanoparticles. Some studies have shown that nanoparticles can have an impact on the aggregation properties of proteins, including fibril formation. Moreover, these studies also show that the capacity of nanoscale objects to induce or prevent misfolding of the proteins strongly depends on the primary structure of the protein. Herein, light is shed on the role of the peptide primary structure in directing nanoparticle‐induced misfolding by means of two model peptides. The design of these peptides is based on the α‐helical coiled‐coil folding motif, but also includes features that enable them to respond to pH changes, thus allowing pH‐dependent β‐sheet formation. Previous studies showed that the two peptides differ in the pH range required for β‐sheet folding. Time‐dependent circular dichroism spectroscopy and transmission electron microscopy are used to characterize peptide folding and aggregate morphology in the presence of negatively charged gold nanoparticles (AuNPs). Both peptides are found to undergo nanoparticle‐induced fibril formation. The determination of binding parameters by isothermal titration calorimetry further reveals that the different propensities of both peptides to form amyloid‐like structures in the presence of AuNPs is primarily due to the binding stoichiometry to the AuNPs. Modification of one of the peptide sequences shows that AuNP‐induced β‐sheet formation is related to the structural propensity of the primary structure and is not a generic feature of peptide sequences with a sufficiently high binding stoichiometry to the nanoparticles.     

Influence of the Thermodynamic and Kinetic Control of Self‐Assembly on the Microstructure Evolution of Silk‐Elastin‐Like Recombinamer Hydrogels

Complex recombinant biomaterials that merge the self‐assembling properties of different (poly)peptides provide a powerful tool for the achievement of specific structures, such as hydrogel networks, by tuning the thermodynamics and kinetics of the system through a tailored molecular design. In this work, elastin‐like (EL) and silk‐like (SL) polypeptides are combined to obtain a silk‐elastin‐like recombinamer (SELR) with dual self‐assembly. First, EL domains force the molecule to undergo a phase transition above a precise temperature, which is driven by entropy and occurs very fast. Then, SL motifs interact through the slow formation of β‐sheets, stabilized by H‐bonds, creating an energy barrier that opposes phase separation. Both events lead to the development of a dynamic microstructure that evolves over time (until a pore size of 49.9 ± 12.7 µm) and to a delayed hydrogel formation (obtained after 2.6 h). Eventually, the network is arrested due to an increase in β‐sheet secondary structures (up to 71.8 ± 0.8%) within SL motifs. This gives a high bond strength that prevents the complete segregation of the SELR from water, which results in a fixed metastable microarchitecture. These porous hydrogels are preliminarily tested as biomimetic niches for the isolation of cells in 3D cultures.     

Electron‐Induced Dynamics of Heptathioether β‐Cyclodextrin Molecules

Variable‐temperature scanning tunneling microscopy (STM) and spectroscopy (STS) measurements are performed on heptathioether β‐cyclodextrin (β‐CD) self‐assembled monolayers (SAMs) on Au. The β‐CD molecules exhibit very rich dynamical behavior, which is not apparent in ensemble‐averaged studies. The dynamics are reflected in the tunneling current–time traces, which are recorded with the STM feedback loop disabled. The dynamics are temperature independent, but increase with increasing tunneling current and sample bias, thus indicating that the conformational changes of the β‐CD molecules are induced by electrons that tunnel inelastically. Even for sample biases as low as 10 mV, well‐defined levels are observed in the tunneling current–time traces. These jumps are attributed to the excitations of the molecular vibration of the macrocyclic β‐CD molecule. The results are of great importance for a proper understanding of transport measurements in SAMs.     

Graphene‐Based Integrated Photovoltaic Energy Harvesting/Storage Device

Energy scavenging has become a fundamental part of ubiquitous sensor networks. Of all the scavenging technologies, solar has the highest power density available. However, the energy source is erratic. Integrating energy conversion and storage devices is a viable route to obtain self‐powered electronic systems which have long‐term maintenance‐free operation. In this work, we demonstrate an integrated‐power‐sheet, consisting of a string of series connected organic photovoltaic cells (OPCs) and graphene supercapacitors on a single substrate, using graphene as a common platform. This results in lighter and more flexible power packs. Graphene is used in different forms and qualities for different functions. Chemical vapor deposition grown high quality graphene is used as a transparent conductor, while solution exfoliated graphene pastes are used as supercapacitor electrodes. Solution‐based coating techniques are used to deposit the separate components onto a single substrate, making the process compatible with roll‐to‐roll manufacture. Eight series connected OPCs based on poly(3‐hexylthiophene)(P3HT):phenyl‐C61‐butyric acid methyl ester (PC₆₀BM) bulk‐heterojunction cells with aluminum electrodes, resulting in a ≈5 V open‐circuit voltage, provide the energy harvesting capability. Supercapacitors based on graphene ink with ≈2.5 mF cm^?2 capacitance provide the energy storage capability. The integrated‐power‐sheet with photovoltaic (PV) energy harvesting and storage functions had a mass of 0.35 g plus the substrate.     

Hierarchical Structure of Silk Materials Versus Mechanical Performance and Mesoscopic Engineering Principles

A comprehensive review on the five levels of hierarchical structures of silk materials and the correlation with macroscopic properties/performance of the silk materials, that is, the toughness, strain‐stiffening, etc., is presented. It follows that the crystalline binding force turns out to be very important in the stabilization of silk materials, while the β‐crystallite networks or nanofibrils and the interactions among helical nanofibrils are two of the most essential structural elements, which to a large extent determine the macroscopic performance of various forms of silk materials. In this context, the characteristic structural factors such as the orientation, size, and density of β‐crystallites are very crucial. It is revealed that the formation of these structural elements is mainly controlled by the intermolecular nucleation of β‐crystallites. Consequently, the rational design and reconstruction of silk materials can be implemented by controlling the molecular nucleation via applying sheering force and seeding (i.e., with carbon nanotubes). In general, the knowledge of the correlation between hierarchical structures and performance provides an understanding of the structural reasons behind the fascinating behaviors of silk materials.     

Coaggregation of κ‐Casein and β‐Lactoglobulin Produces Morphologically Distinct Amyloid Fibrils

The unfolding, misfolding, and aggregation of proteins lead to a variety of structural species. One form is the amyloid fibril, a highly aligned, stable, nanofibrillar structure composed of β‐sheets running perpendicular to the fibril axis. β‐Lactoglobulin (β‐Lg) and κ‐casein (κ‐CN) are two milk proteins that not only individually form amyloid fibrillar aggregates, but can also coaggregate under environmental stress conditions such as elevated temperature. The aggregation between β‐Lg and κ‐CN is proposed to proceed via disulfide bond formation leading to amorphous aggregates, although the exact mechanism is not known. Herein, using a range of biophysical techniques, it is shown that β‐Lg and κ‐CN coaggregate to form morphologically distinct co‐amyloid fibrillar structures, a phenomenon previously limited to protein isoforms from different species or different peptide sequences from an individual protein. A new mechanism of aggregation is proposed whereby β‐Lg and κ‐CN not only form disulfide‐linked aggregates, but also amyloid fibrillar coaggregates. The coaggregation of two structurally unrelated proteins into cofibrils suggests that the mechanism can be a generic feature of protein aggregation as long as the prerequisites for sequence similarity are met.     

Graphene‐Supported Mesoporous Carbons Prepared with Thermally Removable Templates as Efficient Catalysts for Oxygen Electroreduction

Graphene‐supported mesoporous carbons with rich nitrogen self‐doped active sites (N‐MC/rGO) are prepared by direct pyrolysis of a graphene‐oxide‐supported polymer composite embedded with massive, evenly distributed amorphous FeOOH that serve as efficient thermally removable templates. The resulting N‐MC/rGO catalysts exhibit high surface areas and apparent electrocatalytic activity for oxygen reduction reaction in alkaline media. Among the series, the sample prepared at 800 °C displays the best performance with a more positive onset potential, higher limiting currents, much higher stability, and stronger poison resistance than commercial Pt/C. This is ascribed to the synergetic functions of the highly conductive graphene support and the mesoporous N‐doped carbons that effectively impede the restacking of the graphene sheets and enhance the exposure of the rich nitrogen self‐doped active sites.     

Protein‐Bound Freestanding 2D Metal Film for Stealth Information Transmission

The welding and sintering of nanomaterials is usually achieved at high temperatures and high pressures. Here, it is found that merging of metal nanoparticles occurs under ambient conditions in an aqueous solution via protein bonding. It is discovered that the silver nanoparticles from the in situ reduction of silver ammonium ions by glucose undergo confined nucleation and growth and are bound by ultrathin amyloid‐like β‐sheet stacking of lysozyme. This merging of silver nanoparticles creates a freestanding large‐area (e.g., 400 cm²) 2D silver film at the air/water interface with a purity up to 98% and controls nanoscale thickness. This reaction system is general to other proteins and metals, and shows the great ability for controlled synthesis of highly reflective and highly conductive silver films with elongation nearly 10 times higher than that of pure metal without protein bonding. The ultrathin protein‐bonding layer functions as a key mediator to dynamically tune the silver conductance in response to external pressures and strains. The sensors exhibit ultrasensitive capability for stealth transmission of Morse code and for silent speech recording via the detection of tiny vibrations of the human throat. This approach will shed light on the development of protein bonding of a given material for bespoke functions.     

Self‐Defensive Coating for Antibiotics Degradation—Atmospheric Pressure Chemical Vapor Deposition of Functional and Conformal Coatings for the Immobilization of Enzymes

Conformal epoxy‐rich coatings are synthesized by plasma initiated chain‐growth polymerization of glycidyl methacrylate via a newly developed Plasma initiated chemical vapor deposition method at atmospheric pressure to provide a functional platform for the immobilization of enzymes degrading antibiotics (laccase and β‐lactamase). In addition to enhance the enzymes activity duration and intensity, surface immobilization is also leading to enzyme structure rigidification, allowing them to endure mechanical stresses generated by a laminar water flow of 30 km h⁻¹, and this with no reduction of their enzymatic activity. Self‐defensive surface properties against microorganism's adhesion, preventing the enzyme alteration and improving the degradation performances, are obtained via surface saturation with Tween 20. The developed method is scaled up to high specific surface high‐density polyethy­lene biochips commonly used in water treatment, and shows self‐defensive abilities and particularly long lasting efficient degradation properties.     

A Tetrakis(terpyridine) Ligand–Based Cobalt(II) Complex Nanosheet as a Stable Dual‐Ion Battery Cathode Material

Inspired by the flexibility of the bottom‐up approach in terms of selecting molecular components and thus tailoring functionalities, a terpyridine derivative (1,2,4,5‐tetrakis(4‐(2,2′:6′,2″‐terpyridyl)phenyl)benzene) (Tetra‐tpy) is synthesized and coordinated with Co(II) ion to self‐assemble into a nanosheet Co‐sheet by a facile interface‐assisted synthesis. The bis(terpyridine)‐Co(II) complex nanosheet formed not only shows good stability, but also features the layered structure and rich electrochemical activity inherited from the embedded Co(terpyridine)₂ motif. Thus, Co‐sheet can serve as a cathode material for a dual‐ion battery prototype, which exhibits a high utilization of redox‐active sites, good cycling stability, and rate capability, thus expanding the potential application of this kind of easily prepared metal‐complex nanosheets in the field of energy storage.     

Hybrid Nanoscopy of Hybrid Nanomaterials

The combination of complementary techniques to characterize materials at the nanoscale is crucial to gain a more complete picture of their structure, a key step to design and fabricate new materials with improved properties and diverse functions. Here it is shown that correlative atomic force microscopy (AFM) and localization‐based super‐resolution microscopy is a useful tool that provides insight into the structure and emissive properties of fluorescent β‐lactoglobulin (βLG) amyloid‐like fibrils. These hybrid materials are made by functionalization of βLG with organic fluorophores and quantum dots, the latter being relevant for the production of 1D inorganic nanostructures templated by self‐assembling peptides. Simultaneous functionalization of βLG fibers by QD655 and QD525 allows for correlative AFM and two‐color super‐resolution fluorescence imaging of these hybrid materials. These experiments allow the combination of information about the topography and number of filaments that compose a fibril, as well as the emissive properties and nanoscale spatial distribution of the attached fluorophores. This study represents an important step forward in the characterization of multifunctionalized hybrid materials, a key challenge in nanoscience.     

A New Facile Route to Flexible and Semi‐Transparent Electrodes Based on Water Exfoliated Graphene and their Single‐Electrode Triboelectric Nanogenerator

Wearable technologies are driving current research efforts to self‐powered electronics, for which novel high‐performance materials such as graphene and low‐cost fabrication processes are highly sought.The integration of high‐quality graphene films obtained from scalable water processing approaches in emerging applications for flexible and wearable electronics is demonstrated. A novel method for the assembly of shear exfoliated graphene in water, comprising a direct transfer process assisted by evaporation of isopropyl alcohol is developed. It is shown that graphene films can be easily transferred to any target substrate such as paper, flexible polymeric sheets and fibers, glass, and Si substrates. By combining graphene as the electrode and poly(dimethylsiloxane) as the active layer, a flexible and semi‐transparent triboelectric nanogenerator (TENG) is demonstrated for harvesting energy. The results constitute a new step toward the realization of energy harvesting devices that could be integrated with a wide range of wearable and flexible technologies, and opens new possibilities for the use of TENGs in many applications such as electronic skin and wearable electronics.     

A self‐tuning run‐by‐run process controller for processes subject to random disturbances

Abstract

In this paper a self‐tuning run‐by‐run process controller is presented. The controller has the capability of choosing a control parameter dynamically in response to the underlying process disturbances. There are two modules in this controller: a self‐tuning loop trigger module and a run‐by‐run feedback control module. In the self‐tuning loop trigger module, two EWMA control charts are used sequentially to determine if there is a large or medium shift in the process output and to trigger a new self‐tuning loop accordingly. In the run‐by‐run feedback control module, the control parameter and control model are re‐tuned sequentially and a new process recipe is generated, on a run‐by‐run basis, to compensate for the process output's deviation from the target. Monte Carlo simulation results show that the self‐tuning run‐by‐run process controller is superior to the current run‐by‐run process controller with a fixed control parameter.     

Supramolecular Recognition‐Mediated Layer‐by‐Layer Self‐Assembled Gold Nanoparticles for Customized Sensitivity in Paper‐Based Strip Nanobiosensors

Herein, a smart supramolecular self‐assembly‐mediated signal amplification strategy is developed on a paper‐based nanobiosensor to achieve the sensitive and customized detection of biomarkers. The host–guest recognition between β‐cyclodextrin‐coated gold nanoparticles (AuNPs) and 1‐adamantane acetic acid or tetrakis(4‐carboxyphenyl)porphyrin is designed and applied to the layer‐by‐layer self‐assembly of AuNPs at the test area of the strip. Thus, the amplified platform exhibits a high sensitivity with a detection limit at subattogram levels (approximately dozens of molecules per strip) and a wide dynamic range of concentration over seven orders of magnitude. The applicability and universality of this sensitive platform are demonstrated in clinically significant ranges to measure carcinoembryonic antigen and HIV‐1 capsid p24 antigen in spiked serum and clinical samples. The customized biomarker detection ability for the on‐demand needs of clinicians is further verified through cycle incubation‐mediated controllable self‐assembly. Collectively, the supramolecular self‐assembly amplification method is suitable as a universal point‐of‐care diagnostic tool and can be readily adapted as a platform technology for the sensitive assay of many different target analytes.