Tuning the Amphiphilicity of Building Blocks: Controlled Self‐Assembly and Disassembly for Functional Supramolecular Materials

Amphiphilicity is one of the molecular bases for self‐assembly. By tuning the amphiphilicity of building blocks, controllable self‐assembly can be realized. This article reviews different routes for tuning amphiphilicity and discusses different possibilities for self‐assembly and disassembly in a controlled manner. In general, this includes irreversible and reversible routes. The irreversible routes concern irreversible reactions taking place on the building blocks and changing their molecular amphiphilicity. The building blocks are then able to self‐assemble to form different supramolecular structures, but cannot remain stable upon loss of amphiphilicity. Compared to the irreversible routes, the reversible routes are more attractive due to the good control over the assembly and disassembly of the supramolecular structure formed via tuning of the amphiphilicity. These routes involve reversible chemical reactions and supramolecular approaches, and different external stimuli can be used to trigger reversible changes of amphiphilicity, including light, redox, pH, and enzymes. It is anticipated that this line of research can lead to the fabrication of new functional supramolecular assemblies and materials.     

Local Mechanical Perturbation Provides an Effective Means to Regulate the Growth and Assembly of Functional Peptide Fibrils

Mucin 1 (MUC1) peptide fused with Q11 (MUC1‐Q11) having 35 residues has previously been shown to form amyloid fibrils. Using time‐dependent and high‐resolution atomic force microscopy (AFM) imaging, it is revealed that the formation of individual MUC1‐Q11 fibrils entails nucleation and extension at both ends. This process can be altered by local mechanical perturbations using AFM probes. This work reports two specific perturbations and outcomes. First, by increasing load while maintaining tip‐surface contact, the fibrils are cut during the scan due to shearing. Growth of fibrils occurs at the newly exposed termini, following similar mechanism of the MUC1‐Q11 nucleation growth. As a result, branched fibrils are seen on the surface whose orientation and length can be controlled by the nuclei orientation and reaction time. In contrast to the “one‐time‐cut”, fibrils can be continuously fragmented by modulation at sufficiently high amplitude. As a result, short and highly branched fibrils accumulate and pile on surfaces. Since the fibril formation and assembly of MUC1‐Q11 can be impacted by local mechanical force, this approach offers a nonchemical and label‐free means to control the presentation of MUC1 epitopes, and has promising application in MUC1 fibril‐based immunotherapy.     

The Pathway to Intelligence: Using Stimuli‐Responsive Materials as Building Blocks for Constructing Smart and Functional Systems

Systems that are intelligent have the ability to sense their surroundings, analyze, and respond accordingly. In nature, many biological systems are considered intelligent (e.g., humans, animals, and cells). For man‐made systems, artificial intelligence is achieved by massively sophisticated electronic machines (e.g., computers and robots operated by advanced algorithms). On the other hand, freestanding materials (i.e., not tethered to a power supply) are usually passive and static. Hence, herein, the question is asked: can materials be fabricated so that they are intelligent? One promising approach is to use stimuli‐responsive materials; these “smart” materials use the energy supplied by a stimulus available from the surrounding for performing a corresponding action. After decades of research, many interesting stimuli‐responsive materials that can sense and perform smart functions have been developed. Classes of functions discussed include practical functions (e.g., targeting and motion), regulatory functions (e.g., self‐regulation and amplification), and analytical processing functions (e.g., memory and computing). The pathway toward creating truly intelligent materials can involve incorporating a combination of these different types of functions into a single integrated system by using stimuli‐responsive materials as the basic building blocks.     

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.     

Amyloid Fibrils Aerogel for Sustainable Removal of Organic Contaminants from Water

Water contamination by organic pollutants is ubiquitous and hence a global concern due to detrimental effects on the environment and human health. Here, it is demonstrated that amyloid fibrils aerogels are ideal adsorbers for removing organic pollutants from water. To this end, amyloid fibrils prepared from β‑lactoglobulin, the major constituent of milk whey protein, are used as building blocks for the fabrication of the aerogels. The adsorption of Bentazone, Bisphenol A, and Ibuprofen, as model pollutants, is evaluated under quasi-static conditions, without use of energy or pressure. Through adsorption by amyloid fibrils aerogel, excellent removal efficiencies of 92%, 78%, and 98% are demonstrated for Bentazone, Bisphenol A, and Ibuprofen, respectively. Furthermore, the maximum adsorption capacity of amyloid fibrils aerogel for Bentazone, Bisphenol A, and Ibuprofen is 54.2, 50.6, and 69.6 mg g⁻¹, respectively. To shed light on the adsorption equilibrium process, adsorption isotherms, binding constants, saturation limits, and the effect of pH are evaluated. Finally, the regeneration of the aerogel over three consecutive cycles is studied, exhibiting high reusability with no significant changes in its removal performance. These results point at amyloid fibrils aerogels as a sustainable, efficient, and inexpensive technology for alleviating the ubiquitous water contamination by organic pollutants.     

Thioflavin T‐Amyloid Hybrid Nanostructure for Biocatalytic Photosynthesis

Amyloidogenic peptides can self‐assemble into highly ordered nanostructures consisting of cross β‐sheet‐rich networks that exhibit unique physicochemical properties and high stability. Light‐harvesting amyloid nanofibrils are constructed by employing insulin as a building block and thioflavin T (ThT) as a amyloid‐specific photosensitizer. The ability of the self‐assembled amyloid scaffold to accommodate and align ThT in high density on its surface allows for efficient energy transfer from the chromophores to the catalytic units in a similar way to natural photosystems. Insulin nanofibrils significantly enhance the photoactivity of ThT by inhibiting nonradiative conformational relaxation around the central C? C bonds and narrowing the distance between ThT molecules that are bound to the β‐sheet‐rich amyloid structure. It is demonstrated that the ThT‐amyloid hybrid nanostructure is suitable for biocatalytic solar‐to‐chemical conversion by integrating the light‐harvesting amyloid module (for nicotinamide cofactor regeneration) with a redox biocatalytic module (for enzymatic reduction).     

Spatially Controlled Amyloid Reactions Using Organic Electronics

Abnormal protein aggregates, so called amyloid fibrils, are mainly known as pathological hallmarks of a wide range of diseases, but in addition these robust well‐ordered self‐assembled natural nanostructures can also be utilized for creating distinct nanomaterials for bioelectronic devices. However, current methods for producing amyloid fibrils in vitro offer no spatial control. Herein, we demonstrate a new way to produce and spatially control the assembly of amyloid‐like structures using an organic electronic ion pump (OEIP) to pump distinct cations to a reservoir containing a negatively charged polypeptide. The morphology and kinetics of the created proteinaceous nanomaterials depends on the ion and current used, which we leveraged to create layers incorporating different conjugated thiophene derivatives, one fluorescent (p‐FTAA) and one conducting (PEDOT‐S). We anticipate that this new application for the OEIP will be useful for both biological studies of amyloid assembly and fibrillogenesis as well as for creating new bioelectronic nanomaterials and devices.     

Functional Materials and Systems for Rewritable Paper

“Paper” has greatly contributed to the development and spread of civilization. Even in today's “digitalized” world, paper continues to play a key role in socioeconomic growth, as is evidenced by the growth in global paper consumption. Unfortunately, the use of paper has its cost in terms of the exhaustion of world's natural resources. Consequently, new, cost‐effective technologies that preserve natural resources are required for this purpose. Functional materials have revolutionized the way people think about developing new technologies. Especially important in this regard are “smart reactive materials,” which are capable of actively responding to external stimuli such as heat, light, mechanical stress, and specific molecular orientations. Moreover, functionalized chromogenic materials, which undergo reversible color switching upon external stimulation, have attracted great attention in the context of developing rewritable paper. Here, investigations of various materials and systems that are devised for use as rewritable paper are reviewed with the hope that the coverage will stimulate and guide future studies in this area.     

Nucleic Acids and Smart Materials: Advanced Building Blocks for Logic Systems

Logic gates can convert input signals into a defined output signal, which is the fundamental basis of computing. Inspired by molecular switching from one state to another under an external stimulus, molecular logic gates are explored extensively and recognized as an alternative to traditional silicon‐based computing. Among various building blocks of molecular logic gates, nucleic acid attracts special attention owing to its specific recognition abilities and structural features. Functional materials with unique physical and chemical properties offer significant advantages and are used in many fields. The integration of nucleic acids and functional materials is expected to bring about several new phenomena. In this Progress Report, recent progress in the construction of logic gates by combining the properties of a range of smart materials with nucleic acids is introduced. According to the structural characteristics and composition, functional materials are categorized into three classes: polymers, noble‐metal nanomaterials, and inorganic nanomaterials. Furthermore, the unsolved problems and future challenges in the construction of logic gates are discussed. It is hoped that broader interests in introducing new smart materials into the field are inspired and tangible applications for these constructs are found.     

A S‐Layer Protein of Bacillus anthracis as a Building Block for Functional Protein Arrays by In Vitro Self‐Assembly

S‐layer proteins create a cell‐surface layer architecture in both bacteria and archaea. Because S‐layer proteins self‐assemble into a native‐like S‐layer crystalline structure in vitro, they are attractive building blocks in nanotechnology. Here, the potential use of the S‐layer protein EA1 from Bacillus anthracis in constructing a functional nanostructure is investigated, and apply this nanostructure in a proof‐of‐principle study for serological diagnosis of anthrax. EA1 is genetically fused with methyl parathion hydrolase (MPH), to degrade methyl parathion and provide a label for signal amplification. EA1 not only serves as a nanocarrier, but also as a specific antigen to capture anthrax‐specific antibodies. As results, purified EA1–MPH forms a single layer of crystalline nanostructure through self‐assembly. Our chimeric nanocatalyst greatly improves enzymatic stability of MPH. When applied to the detection of anthrax‐specific antibodies in serum samples, the detection of our EA1–MPH nanostructure is nearly 300 times more sensitive than that of the unassembled complex. Together, it is shown that it is possible to build a functional and highly sensitive nanosensor based on S‐layer protein. In conclusion, our present study should serve as a model for the development of other multifunctional nanomaterials using S‐layer proteins.     

25th Anniversary Article: Reversible and Adaptive Functional Supramolecular Materials: “Noncovalent Interaction” Matters

Supramolecular materials held together by noncovalent interactions, such as hydrogen bonding, host–guest interactions, and electrostatic interactions, have great potential in material science. The unique reversibility and adaptivity of noncovalent intreractions have brought about fascinating new functions that are not available by their covalent counterparts and have greatly enriched the realm of functional materials. This review article aims to highlight the very recent and important progresses in the area of functional supramoleuclar materials, focusing on adaptive mechanical materials, smart sensors with enhanced selectivity, soft luminescent and electronic nanomaterials, and biomimetic and biomedical materials with tailored structures and functions. We cannot write a complete account of all the interesting work in this area in one article, but we hope that it can in a way reflect the current situation and future trends in this prosperously developing area of functional supramolecular materials.     

Multifunctional Nanoparticles Self‐Assembled from Small Organic Building Blocks for Biomedicine

Supramolecular self‐assembly shows significant potential to construct responsive materials. By tailoring the structural parameters of organic building blocks, nanosystems can be fabricated, whose performance in catalysis, energy storage and conversion, and biomedicine has been explored. Since small organic building blocks are structurally simple, easily modified, and reproducible, they are frequently employed in supramolecular self‐assembly and materials science. The dynamic and adaptive nature of self‐assembled nanoarchitectures affords an enhanced sensitivity to the changes in environmental conditions, favoring their applications in controllable drug release and bioimaging. Here, recent significant research advancements of small‐organic‐molecule self‐assembled nanoarchitectures toward biomedical applications are highlighted. Functionalized assemblies, mainly including vesicles, nanoparticles, and micelles are categorized according to their topological morphologies and functions. These nanoarchitectures with different topologies possess distinguishing advantages in biological applications, well incarnating the structure–property relationship. By presenting some important discoveries, three domains of these nanoarchitectures in biomedical research are covered, including biosensors, bioimaging, and controlled release/therapy. The strategies regarding how to design and characterize organic assemblies to exhibit biomedical applications are also discussed. Up‐to‐date research developments in the field are provided and research challenges to be overcome in future studies are revealed.