Capillarity induced large area patterning of peptide nanowires

Peptide nanostructures assembled from an aromatic diphenylalanine have attracted considerable attention because of high thermal and mechanical stabilities of the assembled morphologies. Of diverse assembled structures, liquid crystalline peptide nanowires exhibiting optical and mechanical anisotropies can be a valuable building block for micro- or nano-fluidics, molecular electronics, and biological sensing. In this work, we investigated large scale patterning of liquid crystalline peptide nanowires and pattern transfer. The peptide nanowires could be highly aligned on a substrate by capillary flow over a large area. The high etching resistivity of nanowires to subsequent reactive ion etching process allowed for a successful pattern transfer of the well-aligned nanowire morphology onto the underlying SiO2 substrate.     

Hierarchical, interface-induced self-assembly of diphenylalanine: formation of peptide nanofibers and microvesicles

To gain insight into the hierarchical self-assembly of peptides and the surface effect on assembly formation, an aromatic peptide of diphenylalanine (FF) was used in this study as the model peptide. We found that the diphenylalanine peptide could self-assemble into a core-branched nanostructure through non-covalent interactions in aqueous solution. The pre-assemblies further assembled into nanofibers and microvesicles on the glass surface and microporous membrane, respectively, showing a significant dependence on surface characteristics. The structural and morphological differences between nanofibers and microvesicles were investigated directly using several spectroscopy and microscopy techniques. Our results revealed a hierarchical and interface-induced assembly behavior of diphenylalanine peptide. The novel strategy based on the surface effect allows one to controllably fabricate various peptide-based nanostructures.     

Cover Picture: A Micropatterned Hydrogel Platform for Chemical Synthesis and Biological Analysis (Adv. Mater. 5/2006)

A polymer hydrogel platform for peptide arrays compatible with both solid‐phase peptide synthesis conditions and the aqueous environment essential for biological assays is reported on p. 655 by Ulijn and co‐workers. Micropatterning followed by multiple‐step peptide synthesis produces the peptide‐functionalized poly(ethylene glycol)–polyamide “biochips” shown schematically on the cover. On‐chip biological assays involving cells and enzymes provide proof‐of‐concept.     

Peptide‐Based Nanotubes and Their Applications in Bionanotechnology

In nature, biological nanomaterials are synthesized under ambient conditions in a natural microscopic‐sized laboratory, such as a cell. Biological molecules, such as peptides and proteins, undergo self‐assembly processes in vivo and in vitro, and these monomers are assembled into various nanometer‐scale structures at room temperature and atmospheric pressure. The self‐assembled peptide nanostructures can be further organized to form nanowires, nanotubes, and nanoparticles via their molecular‐recognition functions. The application of molecular self‐assemblies of synthetic peptides as nanometer‐scale building blocks in devices is robust, practical, and affordable due to their advantages of reproducibility, large‐scale production ability, monodispersity, and simpler experimental methods. It is also beneficial that smart functionalities can be added at desired positions in peptide nanotubes through well‐established chemical and peptide syntheses. These features of peptide‐based nanotubes are the driving force for investigating and developing peptide nanotube assemblies for biological and non‐biological applications.     

Bioinspired Flexible and Tough Layered Peptide Crystals

One major challenge of functional material fabrication is combining flexibility, strength, and toughness. In several biological and artificial systems, these desired mechanical properties are achieved by hierarchical architectures and various forms of anisotropy, as found in bones and nacre. Here, it is reported that crystals of N‐capped diphenylalanine, one of the most studied self‐assembling systems in nanotechnology, exhibit well‐ordered packing and diffraction of sub‐Å resolution, yet display an exceptionally flexible nature. To explore this flexibility, the mechanical properties of individual crystals are evaluated, assisted by density functional theory calculations. High‐resolution scanning electron microscopy reveals that the crystals are composed of layered self‐assembled structures. The observed combination of strength, toughness, and flexibility can therefore be explained in terms of weak interactions between rigid layers. These crystals represent a novel class of self‐assembled layered materials, which can be utilized for various technological applications, where a combination of usually contradictory mechanical properties is desired.     

Programmable Construction of Peptide‐Based Materials in Living Subjects: From Modular Design and Morphological Control to Theranostics

Self‐assembled nanomaterials show potential high efficiency as theranostics for high‐performance bioimaging and disease treatment. However, the superstructures of pre‐assembled nanomaterials may change in the complicated physiological conditions, resulting in compromised properties and/or biofunctions. Taking advantage of chemical self‐assembly and biomedicine, a new strategy of “in vivo self‐assembly” is proposed to in situ construct functional nanomaterials in living subjects to explore new biological effects. Herein, recent advances on peptide‐based nanomaterials constructed by the in vivo self‐assembly strategy are summarized. Modular peptide building blocks with various functions, such as targeting, self‐assembly, tailoring, and biofunctional motifs, are employed for the construction of nanomaterials. Then, self‐assembly of these building blocks in living systems to construct various morphologies of nanostructures and corresponding unique biological effects, such as assembly/aggregation‐induced retention (AIR), are introduced, followed by their applications in high‐performance drug delivery and bioimaging. Finally, an outlook and perspective toward future developments of in vivo self‐assembled peptide‐based nanomaterials for translational medicine are concluded.     

Cation–π Interaction Trigger Supramolecular Hydrogelation of Peptide Amphiphiles

As an important noncovalent interaction, cation–π interaction plays an essential role in a broad area of biology and chemistry. Despite extensive studies in protein stability and molecular recognition, the utilization of cation–π interaction as a major driving force to construct supramolecular hydrogel remains uncharted. Here, a series of peptide amphiphiles are designed with cation–π interaction pairs that can self-assemble into supramolecular hydrogel under physiological condition. The influence of cation–π interaction is thoroughly investigated on peptide folding propensity, morphology, and rigidity of the resultant hydrogel. Computational and experimental results confirm that cation–π interaction could serve as a major driving force to trigger peptide folding, resultant β-hairpin peptide self-assembled into fibril-rich hydrogel. Furthermore, the designed peptides exhibit high efficacy on cytosolic protein delivery. As the first case of using cation–π interactions to trigger peptide self-assembly and hydrogelation, this work provides a novel strategy to generate supramolecular biomaterials.     

Biological and chemical decoration of peptide nanostructures via biotin-avidin interactions

Novel architectures with nanometric dimensions hold an immense promise as building blocks for future nanotechnological applications. Biological nanostructures are of special interest due to their biocompatibility and because they allow the utilization of biochemical recognition interfaces. The ability to decorate bio-nanostructures with functional groups is highly important in order to utilize them in several applications including ultrasensitive sensors, drug delivery systems, and tissue engineering. Peptide-based nanostructures have a distinct advantage over other assemblies because they can be easily modified with chemical and biological elements. Aromatic dipeptide nanotubes (ADNT) are formed by the self-assembly of a very simple building block, the diphenylalanine peptide. These nanotubes have remarkable chemical and mechanical properties and their utilization in various applications has previously been demonstrated. Here we report on the chemical modification of ADNT with biotin moieties, in order to enable the selective decoration of the tubes with avidin-labeled species. First, ADNT were prepared in aqueous solution by self-assembly of the dipeptide building blocks. Next, they were modified using N-hydroxysuccinimido-biotin. The level of biotinylation was assessed by the interaction of the tubes with gold-labeled strepavidin and ultrastructural analysis by electron microscopy. The ability of the modified assemblies to serve as a generic functional platform was demonstrated by avidin-mediated conjugation. Avidin was added as a molecular linker to allow the decoration with biotin-labeled quantum dots. The efficient decoration was again probed by the imaging of the modified tubes using laser confocal microscopy. Taken together, we demonstrated the ability to decorate ADNT using a generic avidin-biotin adaptor. This decoration should lead to the integration and utilization of the tubes in various applications.     

Bioinspired peptide nanotubes as supercapacitor electrodes

Bioinspired materials offer new routes in nanotechnology. These materials are composed from chemically synthesized biomolecules and inspired by natural biological structures. They are self assembled into highly ordered nanostructures (nanotubes, nanospheres, etc.) from elementary building blocks of biological origin such as peptide and proteins. We developed a new technique of physical vapor deposition of peptide nanotubes (PNT) and applied it to electrochemical energy storage devices—supercapacitors (SC). In this work, aligned and homogenously distributed diphenylalanine PNT have been used to modify carbon electrodes for SC devices. Electrochemical properties of PNT coatings of different density and height, modifying carbon electrodes have been studied. We have found that aligned PNT arrays significantly increase the double layer capacitance of the carbon electrodes. The found enlargement of the PNT-modified electrode capacitance has been ascribed to increasing of usable electrode surface area of the carbon electrodes coated by PNT. We show that the critical factor of the accumulation process of the electrolyte ions at the PNT-modified electrode surface is a wetting process of the PNT nanoscale hydrophilic channels by aqueous electrolyte.     

Supramolecular Materials via Block Copolymer Self‐Assembly

This review discusses the potential of block copolymer type macromolecular building blocks for the preparation of self‐assembled materials. Three different classes of block copolymer type architectures will be distinguished: (i) coil–coil diblock copolymers, (ii) rod–coil diblock copolymers, and (iii) rod–coil diblock oligomers. The basic principles that underlie the self‐assembly of each of these different building blocks will be discussed. These theoretical considerations are complemented with examples from recent literature that illustrate the potential of the different types of block copolymers to prepare (functional) supramolecular materials. Finally, several strategies will be presented that could allow the preparation of stimuli‐sensitive self‐assembled materials, i.e., materials whose properties can be reversibly manipulated under the action of appropriate external stimuli.     

Capillary Force‐Driven,Hierarchical Co‐Assembly of Dandelion‐Like Peptide Microstructures

The wetting and drying of drops on flexible fibers occurs ubiquitously in nature, and the capillary force underlying this phenomenon has motivated our great interest in learning how to direct supramolecular self‐assembly. Here, the hierarchical co‐assembly of two aromatic peptides, diphenylalanine (FF) and ferrocene‐diphenylalanine (Fc‐FF), is reported via sequential, combinatorial assembly. The resulting dandelion‐like microstructures have highly complex architectures, where FF microtube arrays serve as the scapes and the Fc‐FF nanofibers serve as the flower heads. Homogeneous FF microtubes with diameters tailored between 1 and 9 μm and wall thickness ranging from 70 to 950 nm are initially formed by controlling the degree of supersaturation of the FF and the water content. Once the FF microtubes are formed, the growth of the dandelion‐like microstructures is then driven by the capillary force, derived from the wetting and drying of the Fc‐FF solution on the FF microtubes. This simple and ingenious strategy offers many opportunities to develop new and creative methods for controlling the hierarchical self‐assembly of peptides and thus building highly complex nano and microstructures.     

Self‐Assembled Peptide‐Based Nanomaterials for Biomedical Imaging and Therapy

Peptide‐based materials are one of the most important biomaterials, with diverse structures and functionalities. Over the past few decades, a self‐assembly strategy is introduced to construct peptide‐based nanomaterials, which can form well‐controlled superstructures with high stability and multivalent effect. More recently, peptide‐based functional biomaterials are widely utilized in clinical applications. However, there is no comprehensive review article that summarizes this growing area, from fundamental research to clinic translation. In this review, the recent progress of peptide‐based materials, from molecular building block peptides and self‐assembly driving forces, to biomedical and clinical applications is systematically summarized. Ex situ and in situ constructed nanomaterials based on functional peptides are presented. The advantages of intelligent in situ construction of peptide‐based nanomaterials in vivo are emphasized, including construction strategy, nanostructure modulation, and biomedical effects. This review highlights the importance of self‐assembled peptide nanostructures for nanomedicine and can facilitate further knowledge and understanding of these nanosystems toward clinical translation.     

Direct Synthesis of the 2D Copper(II) 5‐Prop‐2‐ynoxyisophthalate MOF: Comment on “Surface Functionalization of Porous Coordination Nanocages Via Click Chemistry and Their Application in Drug Delivery”

Synthesis of metal–organic materials is often dependent on the reaction conditions of suitable solvent/solvent mixture and temperature. A new finding based on a previously described protocol is reported: instead of obtaining metal–organic polyhedra (MOP), a metal–organic framework (MOF) with a 2D layered structure is obtained, following the same reported protocol. The 2D Cu(II)–5‐prop‐2‐ynoxyisophthlate MOF, crystallized in a kagomé‐type structure, is synthesized using different solvent systems at room temperature, as well as under solvothermal (nonhydrothermal) conditions. Under harsh reaction conditions, alkyne functional groups maintain their integrity and the copper does not catalyze the oxidative coupling of the terminal alkyne groups. X‐ray diffraction analyses confirm the structure and phase purity of the product. Based on the present results and the previous work reported by Zhao et al., it seems that two products, namely 0D MOP and 2D MOF, are equally possible when using the same reactants under same reaction conditions. However, the materials obtained in all the trials are MOF instead of MOP. From the structure point of view, there is a difference in connectivity of the initial building units that determines whether the product is MOP or MOF.     

Multiphase Assembly of Small Molecule Microcrystalline Peptide Hydrogel Allows Immunomodulatory Combination Therapy for Long‐Term Heart Transplant Survival

Combination therapies that target multiple pathways involved in immune rejection of transplants hold promise for patients in need of restorative surgery. Herein, a noninteracting multiphase molecular assembly approach is developed to crystallize tofacitinib, a potent JAK1/3 inhibitor, within a shear‐thinning self‐assembled fibrillar peptide hydrogel network. The resulting microcrystalline tofacitinib hydrogel (MTH) can be syringe‐injected directly to the grafting site during surgery to locally deliver the small molecule. The rate of drug delivered from MTH is largely controlled by the dissolution of the encapsulated microcrystals. A single application of MTH, in combination with systemically delivered CTLA4‐Ig, a co‐stimulation inhibitor, affords significant graft survival in mice receiving heterotopic heart transplants. Locoregional studies indicate that the local delivery of tofacitinib at the graft site enabled by MTH is required for the observed enhanced graft survival.     

Amino Acids and Peptide‐Based Supramolecular Hydrogels for Three‐Dimensional Cell Culture

Supramolecular hydrogels assembled from amino acids and peptide‐derived hydrogelators have shown great potential as biomimetic three‐dimensional (3D) extracellular matrices because of their merits over conventional polymeric hydrogels, such as non‐covalent or physical interactions, controllable self‐assembly, and biocompatibility. These merits enable hydrogels to be made not only by using external stimuli, but also under physiological conditions by rationally designing gelator structures, as well as in situ encapsulation of cells into hydrogels for 3D culture. This review will assess current progress in the preparation of amino acids and peptide‐based hydrogels under various kinds of external stimuli, and in situ encapsulation of cells into the hydrogels, with a focus on understanding the associations between their structures, properties, and functions during cell culture, and the remaining challenges in this field. The amino acids and peptide‐based hydrogelators with rationally designed structures have promising applications in the fields of regenerative medicine, tissue engineering, and pre‐clinical evaluation.     

Unusual Two-Step Assembly of a Minimalistic Dipeptide-Based Functional Hypergelator

Self-assembled peptide hydrogels represent the realization of peptide nanotechnology into biomedical products. There is a continuous quest to identify the simplest building blocks and optimize their critical gelation concentration (CGC). Herein, a minimalistic, de novo dipeptide, Fmoc-Lys(Fmoc)-Asp, as an hydrogelator with the lowest CGC ever reported, almost fourfold lower as compared to that of a large hexadecapeptide previously described, is reported. The dipeptide self-assembles through an unusual and unprecedented two-step process as elucidated by solid-state NMR and molecular dynamics simulation. The hydrogel is cytocompatible and supports 2D/3D cell growth. Conductive composite gels composed of Fmoc-Lys(Fmoc)-Asp and a conductive polymer exhibit excellent DNA binding. Fmoc-Lys(Fmoc)-Asp exhibits the lowest CGC and highest mechanical properties when compared to a library of dipeptide analogues, thus validating the uniqueness of the molecular design which confers useful properties for various potential applications.     

Directed Self‐Assembly of Star‐Block Copolymers by Topographic Nanopatterns through Nucleation and Growth Mechanism

Exploring the ordering mechanism and dynamics of self‐assembled block copolymer (BCP) thin films under confined conditions are highly essential in the application of BCP lithography. In this study, it is aimed to examine the self‐assembling mechanism and kinetics of silicon‐containing 3‐arm star‐block copolymer composed of polystyrene (PS) and poly(dimethylsiloxane) blocks as nanostructured thin films with perpendicular cylinders and controlled lateral ordering by directed self‐assembly using topographically patterned substrates. The ordering process of the star‐block copolymer within fabricated topographic patterns with PS‐functionalized sidewall can be carried out through the type of secondary (i.e., heterogeneous) nucleation for microphase separation initiated from the edge and/or corner of the topographic patterns, and directed to grow as well‐ordered hexagonally packed perpendicular cylinders. The growth rate for the confined microphase separation is highly dependent upon the dimension and also the geometric texture of the preformed pattern. Fast self‐assembly for ordering of BCP thin film can be achieved by lowering the confinement dimension and also increasing the concern number of the preformed pattern, providing a new strategy for the design of BCP lithography from the integration of top‐down and bottom‐up approaches.     

A Highly Stretchable and Real‐Time Healable Supercapacitor

In addition to a high specific capacitance, a large stretchability and self‐healing properties are also essential to improve the practicality and reliability of supercapacitors in portable and wearable electronics. However, the integration of multiple functions into one device remains challenging. Here, the construction of a highly stretchable and real‐time omni‐healable supercapacitor is demonstrated by sandwiching the polypyrrole‐incorporated gold nanoparticle/carbon nanotube (CNT)/poly(acrylamide) (GCP@PPy) hydrogel electrodes with a CNT‐free GCP (GP) hydrogel as the electrolyte and chemically soldering an Ag nanowire film to the hydrogel electrode as the current collector. The newly developed dynamic metal‐thiolate (M‐SR, M = Au, Ag) bond‐induced integrated configuration, with an intrinsically powerful electrode and electrolyte, enables the assembled supercapacitor to deliver an areal capacitance of 885 mF cm^?2 and an energy density of 123 µWh cm^?2, which are among the highest‐reported values for stretchable supercapacitors. Notably, the device exhibits a superhigh stretching strain of 800%, rapid optical healing capability, and significant real‐time healability during the charge–discharge process. The exceptional performance combined with the facile assembly method confirms this multifunctional device as the best performer among all the flexible supercapacitors reported to date.     

Semi-wet peptide/protein array using supramolecular hydrogel

The protein microarray is a crucial biomaterial for the rapid and high-throughput assay of many biological events where proteins are involved. In contrast to the DNA microarray, it has not been sufficiently established because of protein instability under the conventional dry conditions. Here we report a novel semi-wet peptide/protein microarray using a supramolecular hydrogel composed of glycosylated amino acetate. The spontaneous gel-formation and amphiphilic properties of this supramolecular hydrogel have been applied to a new type of peptide/protein gel array that is compatible with enzyme assays. Aqueous cavities created in the gel matrix are a suitable semi-wet reaction medium for enzymes, whereas the hydrophobic domains of the fibre are useful as a unique site for monitoring the reaction. This array system overcomes several drawbacks of conventional protein chips, and thus can have potential applications in pharmaceutical research and diagnosis.     

Fingerprinting of Peptides with a Large Channel of Bacteriophage Phi29 DNA Packaging Motor

Nanopore technology has become a highly sensitive and powerful tool for single molecule sensing of chemicals and biopolymers. Protein pores have the advantages of size amenability, channel homogeneity, and fabrication reproducibility. But most well‐studied protein pores for sensing are too small for passage of peptide analytes that are typically a few nanometers in dimension. The funnel‐shaped channel of bacteriophage phi29 DNA packaging motor has previously been inserted into a lipid membrane to serve as a larger pore with a narrowest N‐terminal constriction of 3.6 nm and a wider C‐terminal end of 6 nm. Here, the utility of phi29 motor channel for fingerprinting of various peptides using single molecule electrophysiological assays is reported. The translocation of peptides is proved unequivocally by single molecule fluorescence imaging. Current blockage percentage and distinctive current signatures are used to distinguish peptides with high confidence. Each peptide generated one or two distinct current blockage peaks, serving as typical fingerprint for each peptide. The oligomeric states of peptides can also be studied in real time at single molecule level. The results demonstrate the potential for further development of phi29 motor channel for detection of disease‐associated peptide biomarkers.