Functional Organic Semiconductors Assembled via Natural Aggregating Peptides

Specific peptide sequences designed by inspection of protein–protein interfaces have been identified and used as tectons in hybrid functional materials. Here, an 8‐mer peptide derived from an interface of the peroxiredoxin family of self‐assembling proteins is exploited to encode the assembly of the perylene imide‐based organic semiconductor building blocks. By augmenting the peptide with additional functionality to trigger aggregation and manipulate the directionality of peptide‐semiconductor coupling, a series of hybrid materials based on the natural peptide interface is presented. Using spectroscopic probes, the mode of self‐assembly and the electronic coupling between neighboring perylene units is shown to be strongly affected by the number of peptides attached, and by their backbone directionality. The disubstituted material with peptides extending in the N to C direction away from the perylene core exhibits strong coupling and long‐range order, both attractive properties for electronic device applications. A bio‐organic field‐effect transistor is fabricated using this material, highlighting the possibilities of exploiting natural peptide tectons to encode self‐assembly in other functional materials and devices.     

Formation of Functionalized Nanowires by Control of Self‐Assembly Using Multiple Modified Amyloid Peptides

Amyloid peptides have great potential as building blocks in the creation of functional nanowires due to their natural ability to self‐assemble into nanofibrillar structures and because they can be easily modified with various functional groups. However, significant modifications of an amyloid peptide generally alter its self‐assembly property, making it difficult to construct functionalized fibrils with a desired structure and function. In this study, a very effective method to overcome this problem is demonstrated by using our structure‐controllable amyloid peptides (SCAPs) terminated with a three‐amino‐acid‐residue cap. The method consists on mixing two or more structurally related amyloid peptides with a fraction of modified SCAPs which co‐assemble into a fibril. This SCAP‐mixing method provides remarkable control over the self‐assembly process both on the small oligomers level and the macroscopic fibrils level. Furthermore, it is shown that the modified peptides imbedded in the resulting fibril can subsequently be functionalized to generate nanowires with the desired properties, highlighting the importance of this SCAP method for nanotechnology applications.     

Assemblies of Functional Peptides and Their Applications in Building Blocks for Biosensors

This feature article highlights our recent applications of functional peptide nanotubes, self‐assembled from short peptides with recognition elements, as building blocks to develop sensors. Peptide nanotubes with high aspect ratios are excellent building blocks for a directed assembly into device configurations, and their combined structures with nanometric diameters and micrometric lengths enables to bridge the “nanoworld” and the “microworld”. When the peptide‐nanotube‐based biosensors, which incorporate molecular recognition units, apply alternating current probes to detect impedance signals, the peptide nanotubes behave as excellent building blocks of the transducer for the detection of target analyes such as pathogens, cells, and heavey metal ions with high specificity. In some sensor configurations, the electric signal can be amplified by coupling them with ion‐specific mineralization via molecular recognition of peptides. In general the detection limit of peptide nanotube chips sensors is very low and the dynamic range of detection can be widened by improved device designs.     

Mussel Inspired Dynamic Cross‐Linking of Self‐Healing Peptide Nanofiber Network

A general drawback of supramolecular peptide networks is their weak mechanical properties. In order to overcome a similar challenge, mussels have adapted to a pH‐dependent iron complexation strategy for adhesion and curing. This strategy also provides successful stiffening and self‐healing properties. The present study is inspired by the mussel curing strategy to establish iron cross‐link points in self‐assembled peptide networks. The impact of peptide‐iron complexation on the morphology and secondary structure of the supramolecular nanofibers is characterized by scanning electron microscopy, circular dichroism and Fourier transform infrared spectroscopy. Mechanical properties of the cross‐linked network are probed by small angle oscillatory rheology and nanoindentation by atomic force microscopy. It is shown that iron complexation has no influence on self‐assembly and β‐sheet‐driven elongation of the nanofibers. On the other hand, the organic‐inorganic hybrid network of iron cross‐linked nanofibers demonstrates strong mechanical properties comparable to that of covalently cross‐linked network. Strikingly, iron cross‐linking does not inhibit intrinsic reversibility of supramolecular peptide polymers into disassembled building blocks and the self‐healing ability upon high shear load. The strategy described here could be extended to improve mechanical properties of a wide range of supramolecular polymer networks.     

Fabrication of CdSe‐Nanofibers with Potential for Biomedical Applications

The design and synthesis of nanostructured functional hybrid biomaterials are essential for the next generation of advanced diagnostics and the treatment of disease. A simple route to fabricate semiconductor nanofibers by self‐assembled, elastin‐like polymer (ELP)‐templated semiconductor nanoparticles is reported. Core–shell nanostructures of CdSe nanoparticles with a shell of ELPs are used as building blocks to fabricate functional one‐dimensional (1D) nanostructures. The CdSe particles are generated in situ within the ELP matrix at room temperature. The ELP controls the size and the size‐distribution of the CdSe nanoparticles in an aqueous medium and simultaneously directs the self‐assembly of core–shell building blocks into fibril architectures. It was found that the self‐assembly of core–shell building blocks into nanofibers is strongly dependent on the pH value of the medium. Results of cytotoxicity and antiproliferation of the CdSe‐ELP nanofibers demonstrate that the CdSe‐ELP does not exhibit any toxicity towards B14 cells. Moreover, these are found to be markedly capable of crossing the cell membrane of B14. In contrast, unmodified CdSe nanoparticles with ELPs cause a strong toxic response and reduction in the cell proliferation. This concept is valid for the fabrication of a variety of metallic and semiconductor 1D‐architectures. Therefore, it is believed that these could be used not only for biomedical purposes but for application in a wide range of advanced miniaturized devices.     

Synthetic Self‐Limiting Structures Engineered with Defective Colloidal Clusters

One of the key challenges in the study of self‐assembly with synthetic particles is how to build finite‐sized constructs that resemble self‐limiting structures such as well‐known proteins and biomolecules found in nature. Inspired by this concept, a novel method for realizing self‐limiting self‐assembly of colloidal clusters by establishing design rules to obtain desired final structures using a bottom‐up assembly approach is presented. The constructs identified in this work will be “locked” in a well‐defined configuration as the structure morphologies will not allow them to grow any further. The approach presented here provides two distinct advantages. First, the self‐limiting characteristics of the resulting constructs are preserved no matter how many building blocks are present within the system. Second, the setup of interparticle interactions reflected by interaction matrices are much simpler compared to finite‐sized structures of simple spherical particles which may require engineering pairwise interactions between as many particle types as the number of particles present in the system. The self‐assembly process as well as phase transformation and kinetics of several intriguing finite‐sized configurations are studied. Possible extensions of this concept to produce sophisticated multi‐phased structures where different types of finite‐sized and large assemblies may be present at once are also discussed.     

Hybrid Proton and Electron Transport in Peptide Fibrils

Protons and electrons are being exploited in different natural charge transfer processes. Both types of charge carriers could be, therefore, responsible for charge transport in biomimetic self‐assembled peptide nanostructures. The relative contribution of each type of charge carrier is studied in the present work for fibrils self‐assembled from amyloid‐β derived peptide molecules, in which two non‐natural thiophene‐based amino acids are included. It is shown that under low humidity conditions both electrons and protons contribute to the conduction, with current ratio of 1:2 respectively, while at higher relative humidity proton transport dominates the conductance. This hybrid conduction behavior leads to a bimodal exponential dependence of the conductance on the relative humidity. Furthermore, in both cases the conductance is shown to be affected by the peptide folding state under the entire relative humidity range. This unique hybrid conductivity behavior makes self‐assembled peptide nanostructures powerful building blocks for the construction of electric devices that could use either or both types of charge carriers for their function.     

A Modular Vaccine Platform Combining Self‐Assembled Peptide Cages and Immunogenic Peptides

Subunit vaccines use delivery platforms to present minimal antigenic components for immunization. The benefits of such systems include multivalency, self‐adjuvanting properties, and more specific immune responses. Previously, the design, synthesis, and characterization of self‐assembling peptide cages (SAGEs) have been reported. In these, de novo peptides are combined to make hubs that assemble into nanoparticles when mixed in aqueous solution. Here it is shown that SAGEs are nontoxic particles with potential as accessible synthetic peptide scaffolds for the delivery of immunogenic components. To this end, SAGEs functionalized with the model antigenic peptides tetanus toxoid_632‐651 and ovalbumin_323‐339 drive antigen‐specific responses both in vitro and in vivo, eliciting both CD4⁺ T cell and B cell responses. Additionally, SAGEs functionalized with the antigenic peptide hemagglutinin_518‐526 from the influenza virus are also able to drive a CD8⁺ T cell response in vivo. This work demonstrates the potential of SAGEs to act as a modular scaffold for antigen delivery, capable of inducing and boosting specific and tailored immune responses.     

Guest‐Molecule‐Directed Assembly of Mesostructured Nanocomposite Polymer/Organoclay Hydrogels

Given the urgent need for soft materials with high functional value, hydrogels based on the integrative assembly of organic polymers and nanoscale inorganic building blocks—so‐called nanocomposite polymer hydrogels—offer a generic approach to swollen hybrid networks with tuneable and synergistic properties. Here, we report a new approach to assembling nanocomposite polymer hydrogels with multiple levels of structural complexity and enhanced functionality by using nanoscale integration of mesostructured inorganic building blocks capable of sequestering and releasing drugs (ibuprofen, aspirin, naproxen) and enzymes (glucose oxidase). The viscoelastic materials are produced by noncovalent crosslinking of poly(vinylpyrrolidone) in the presence of low amounts (1–5 wt%) of an exfoliated synthetic organoclay that undergoes in situ guest‐molecule‐directed self‐assembly. The hydrogels can be moulded into shape‐persistent, free‐standing objects that are stable between pH values of 4 to 11 and self‐heal when damaged. Significantly, the mesostructured nanocomposite polymer hydrogels, which can be reversibly dried and reconstituted in the form of highly swollen materials, exhibit sustained drug release and can be recharged and reused. The results provide important guidelines for developing new multifunctional nanocomposite polymer hydrogels based on the concerted self‐assembly of inorganic building blocks with mesostructured interiors.     

Magnetic‐Field‐Induced Phase‐Selective Synthesis of Ferrosulfide Microrods by a Hydrothermal Process: Microstructure Control and Magnetic Properties

Microrods of the ferrosulfide minerals greigite (Fe₃S₄) and marcasite (FeS₂) are selectively synthesized by an in situ magnetic‐field‐assisted hydrothermal route. Each complex microrod is composed of fine building blocks with different shapes. The unique magnetic properties of the microrods and electrical performance of a single microrod are studied. The results demonstrate that the magnetic properties of the ferrosulfide minerals are strongly related to their corresponding microstructures. The value of the low‐temperature transition increases as the greigite component in the product decreases. The combination of small‐molecule sulfur precursors and an applied magnetic field makes possible the selective synthesis of ferrosulfide minerals with different phases and distinct microstructures, underlining the fact that the magnetic field can be a useful tool as well as an independent parameter for the phase‐selective synthesis and self‐assembly of inorganic building blocks in solution chemistry.     

Solvent‐Controlled Assembly of Aromatic Glutamic Dendrimers for Efficient Luminescent Color Conversion

A binary supramolecular system where self‐sorting and coassembly behavior can be switched by changing the solvent polarity is hereby reported. Glutamic dendron is separately conjugated with pyrene and naphthalimide luminophores through an alkyl spacer. The resulting structurally similar building units can self‐assemble into one‐dimensional micro/nanostructures with hexagonal and lamellar packing, respectively. Varying solvents from polar aqueous solution to nonpolar decane is evidenced to profoundly inverse the superchirality and switch self‐sorted assembly to coassembly of the two building blocks. The moisture sensitivity of the naphthalimide moiety is considered the primary driving force for the self‐sorting phenomenon in aqueous solution, resulting in inevitable hydration to repel its stacking with hydrophobic pyrene moiety. On the other hand, the naphthalimide unit can integrate segmentally with the pyrene unit in decane, greatly facilitating the nanofiber growth and supramolecular gel formation along with improved energy transfer efficiency between luminophores. As a result, the coassembly‐based thin films show efficient luminescent color conversion upon the UV light irradiation. This research presents a useful route for the fabrication of controllable solution‐processed light emitting devices from self‐assembled multicomponent systems.     

Nanostructured Surfaces

Many approaches to the structuring of surfaces in the micrometer and nanometer range have been undertaken in the last few decades. Most of these technologies, however, are limited to the fabrication of small areas. In this article two methods for the creation of larger areas of structured surfaces are discussed. The first approach is based on the self‐assembly of ligand‐protected Au₅₅ clusters at the phase boundary between water and dichloromethane, with subsequent transfer to a solid substrate. The other strategy employs nanoporous alumina membranes as masks for the imprinting of metal and polymer surfaces. The self‐assembly generates surfaces with building blocks of about 2 nm (see Figure) whereas the imprinting method leads to structural units of 10–200 nm.     

Integrative Self‐Assembly of Graphene Quantum Dots and Biopolymers into a Versatile Biosensing Toolkit

Hybrid self‐assembly has become a reliable approach to synthesize soft materials with multiple levels of structural complexity and synergistic functionality. In this work, photoluminescent graphene quantum dots (GQDs, 2–5 nm) are used for the first time as molecule‐like building blocks to construct self‐assembled hybrid materials for label‐free biosensors. Ionic self‐assembly of disc‐shaped GQDs and charged biopolymers is found to generate a series of hierarchical structures that exhibit aggregation‐induced fluorescence quenching of the GQDs and change the protein/polypeptide secondary structure. The integration of GQDs and biopolymers via self‐assembly offers a flexible toolkit for the design of label‐free biosensors in which the GQDs serve as a fluorescent probe and the biopolymers provide biological function. The versatility of this approach is demonstrated in the detection of glycosaminoglycans (GAGs), pH, and proteases using three strategies: 1) competitive binding of GAGs to biopolymers, 2) pH‐responsive structural changes of polypeptides, and 3) enzymatic hydrolysis of the protein backbone, respectively. It is anticipated that the integrative self‐assembly of biomolecules and GQDs will open up new avenues for the design of multifunctional biomaterials with combined optoelectronic properties and biological applications.     

Biomimetic Chitin–Silk Hybrids: An Optically Transparent Structural Platform for Wearable Devices and Advanced Electronics

The cuticles of insects and marine crustaceans are fascinating models for man‐made advanced functional composites. The excellent mechanical properties of these biological structures rest on the exquisite self‐assembly of natural ingredients, such as biominerals, polysaccharides, and proteins. Among them, the two commonly found building blocks in the model biocomposites are chitin nanofibers and silk‐like proteins with β‐sheet structure. Despite being wholly organic, the chitinous protein complex plays a key role for the biocomposites by contributing to the overall mechanical robustness and structural integrity. Moreover, the chitinous protein complex alone without biominerals is optically transparent (e.g., dragonfly wings), thereby making it a brilliant model material system for engineering applications where optical transparency is essentially required. Here, inspired by the chitinous protein complex of arthropods cuticles, an optically transparent biomimetic composite that hybridizes chitin nanofibers and silk fibroin (β‐sheet) is introduced, and its potential as a biocompatible structural platform for emerging wearable devices (e.g., smart contact lenses) and advanced displays (e.g., transparent plastic cover window) is demonstrated.     

Porphyrin‐ and Fullerene‐Based Molecular Photovoltaic Devices

We have developed a novel strategy for the construction of molecular photovoltaic devices where the porphyrins and fullerenes employed as building blocks are organized into nanostructured artificial photosynthetic systems by self‐assembly processes. Highly efficient photosynthetic energy‐ and electron‐transfer processes take place at gold and indium tin oxide (ITO) electrodes modified with self‐assembled monolayers of porphyrin‐ or fullerene linked systems. Porphyrins and fullerenes have also been assembled step by step to make large and uniform clusters on nanostructured semiconductor electrodes, which exhibit a high power‐conversion efficiency of close to 1 %. These results will provide valuable information on the design of donor–acceptor‐type molecular assemblies that can be tailored to construct highly efficient photovoltaic devices.     

Thermosensitive Molecular,Colloidal, and Bulk Interactions Using a Simple Surfactant

Efficient use of (nano)particle self‐assembly for creating nanostructured materials requires sensitive control over the interactions between building blocks. Here, a very simple method for rendering the interactions between almost any hydrophobic nano‐ and microparticles thermoswitchable is described and this attraction is characterized using colloid probe atomic force microscopy (CP‐AFM). In a single‐step synthesis, a thermoresponsive surfactant is prepared that through physical adsorption generates a thermosensitive brush on hydrophobic surfaces. These surface layers can reversibly trigger gelation and crystallization of nano‐ and microparticles, and at the same time can be used to destabilize emulsions on demand. The method requires no chemical surface modification yet is universal, reproducible, and fully reversible.     

Co‐Assembled and Microfabricated Bioactive Membranes

The fabrication of hierarchical and bioactive self‐supporting membranes, which integrate physical and biomolecular elements, using a single‐step process that combines molecular self‐assembly with soft lithography is reported. A positively charged multidomain peptide (with or without the cell‐adhesive sequence arginine‐glycine‐aspartic acid‐serine (RGDS)) self‐assembles with hyaluronic acid (HA), an anionic biopolymer. Optimization of the assembling conditions enables the realization of membranes with well‐controlled and easily tunable features at multiple size scales including peptide sequence, building‐block co‐assembly, membrane thickness, bioactive epitope availability, and topographical pattern morphology. Membrane structure, morphology, and bioactivity are investigated according to temperature, assembly time, and variations in the experimental setup. Furthermore, to evaluate the physical and biomolecular signaling of the self‐assembled microfabricated membranes, rat mesenchymal stem cells are cultured on membranes exhibiting various densities of RGDS and different topographical patterns. Cell adhesion, spreading, and morphology are significantly affected by the surface topographical patterns and the different concentrations of RGDS. The versatility of the combined bottom‐up and top‐down fabrication processes described may permit the development of hierarchical macrostructures with precise biomolecular and physical properties and the opportunity to fine tune them with spatiotemporal control.     

Amino Acid Pairing for De Novo Design of Self‐Assembling Peptides and Their Drug Delivery Potential

Molecular self‐assembly has emerged as the “bottom‐up” engineering route to fabricate functional supramolecules for diverse applications. The design of molecular building units becomes critical in determining the structure, properties, and function of the resulting assemblies. Here, a de novo design principle of amino acid pairing (AAP) to generate new classes of self‐assembling peptides (SAPs) is presented. In this study, the AAP focuses on hydrogen bonding, and ionic and hydrophobic interactions among amino acid pairs. With solely hydrogen bond pairs, SAPs can be constructed with only two amino acids. With all three AAP strategies (hydrogen bonds, ionic and hydrophobic pairs), a short novel SAP is constructed. This peptide can self‐assemble into β‐sheet‐rich nanofibers with a relatively low “critical aggregation concentration (CAC)” of ～10 μM . It also shows the ability to stabilize and deliver the hydrophobic anticancer agent ellipticine in aqueous solution. The peptide‐drug complexes/co‐assemblies exhibit anticancer activity against human lung carcinoma cells A549 and breast cancer cells MCF‐7, and have good dilution stability. The presented AAP design provides a new strategy to fabricate functional supramolecules with potential applications in nanomedicine.     

Multiscale Nanoparticle Assembly: From Particulate Precise Manufacturing to Colloidal Processing

Nanoparticle assembly and colloidal processing are two techniques with the goal to fabricate materials and devices from preformed particles. While colloidal processing has become an integral part of ceramic processing, nanoparticle assembly is still mainly limited to academic interests. It typically starts with the precise synthesis of building blocks, which are generally not only considerably smaller than those used for colloidal processing, but also better defined in terms of size, shape, and size distribution. Their arrangement into 1D, 2D, and 3D architectures is performed with great accuracy well beyond what is achieved by colloidal processing. At the same time, the final assembly is not sintered such that the intrinsic, nanospecific properties of the initial building blocks are preserved or even lead to collective behavior. However, in contrast to colloidal processing the structures accessible by nanoparticle assembly are often limited to a small length scale. The review presents selected examples of nanoparticle assembly and colloidal processing with the goal to reveal the capabilities of these two techniques to fabricate novel materials from preformed building blocks, and also to demonstrate the immense opportunities that would arise if the two methods could be combined with each other.     

Self‐Assembling Nanotubes Consisting of Rigid Cyclic γ‐Peptides

Self‐assembling cyclic peptide nanotubes (SPNs) have been extensively studied due to their potential applications in biology and material sciences. Cyclic γ‐peptides, which have a larger conformational space, have received less attention than the cyclic α‐ and β‐peptides. The self‐assembly of cyclic homo‐γ‐tetrapeptide based on cis‐3‐aminocyclohexanecarboxylic acid (γ‐Ach) residues, which can be easily synthesized by a one‐pot process is investigated. Fourier transform infrared (FTIR) and NMR analysis along with density functional theory (DFT) calculations indicate that the cyclic homo‐γ‐tetrapeptide, with a non‐planar conformation, can self‐assemble into nanotubes through hydrogen‐bond‐mediated parallel stacking. Atomic force microscopy (AFM) and transmission electron microscopy (TEM) experiments reveal the formation of bundles of nanotubes in CH₂Cl₂/hexane, but individual nanotubes and bundles of only two nanotubes are obtained in water. The integration of TEG (triethylene glycol) monomethyl ether chains and cyclopeptide backbones may allow the control of width of single nanotubes.