Order/Disorder in Protein and Peptide-Based Biomaterials

Nature utilizes both order and disorder (or controlled disorder) to achieve exceptional materials properties and functions, while synthetic supramolecular materials mostly exploit just supramolecular order, thus limiting the structural diversity, responsiveness and consequent adaptive functions that can be accessed. Herein, we review the emerging field of supramolecular biomaterials where disorder and order deliberately co-exist, and can be dynamically regulated by considering both entropic and enthalpic factors in design. We focus on sequence-structure relationships that govern the (cooperative) assembly pathways of protein and peptide building blocks in these materials. Increasingly, there is an interest in introducing dynamic features in protein and peptide-based structures, such as the remarkable thermo-responsiveness and exceptional mechanical properties of elastin materials. Simultaneously, advances in the field of intrinsically disordered proteins (IDPs) give new insights about their involvement in intracellular liquid-liquid phase separation and formation of disordered, dynamic coacervate structures. These have inspired efforts to design biomaterials with similar dynamic properties. These hybrid ordered/disordered materials employ a combination of intramolecular and supramolecular order/disorder features for construction of assemblies that are dynamically reconfigurable. The assembly of these dynamic structures is mainly entropy-driven, relying on electrostatic and hydrophobic interactions and is mediated in part through the adopted (unstructured) protein conformation or by introducing an oppositely charged guest for peptide building blocks. Examples include design of protein building blocks composed of disordered repeat sequences of elastin-like polypeptides in combination with ordered regions that adopt a secondary structure, the co-assembly of proteins with peptide amphiphiles to achieve reconfigurable, yet highly stable membranes or tyrosine-containing tripeptides with sequence-controlled order/disorder that upon enzymatic oxidation give rise to melanin-like polymeric pigments with customizable properties. The resulting hybrid materials with controlled disorder can be metastable, and sensitive to various external stimuli giving rise to insights that are especially attractive for the design of responsive and adaptive materials.     

Supramolecular Nanofibers of Peptide Amphiphiles for Medicine

Peptide nanostructures are an exciting class of supramolecular systems that can be designed for novel therapies with great potential in advanced medicine. This paper reviews progress on nanostructures based on peptide amphiphiles capable of forming one-dimensional assemblies that emulate in structure the nanofibers present in extracellular matrices. These systems are highly tunable using supramolecular chemistry, and can be designed to signal cells directly with bioactive peptides. Peptide amphiphile nanofibers can also be used to multiplex functions through co-assembly and designed to deliver proteins, nucleic acids, drugs, or cells. We illustrate here the functionality of these systems, describing their use in regenerative medicine of bone, cartilage, the nervous system, the cardiovascular system, and other tissues. In addition, we highlight recent work on the use of peptide amphiphile assemblies to create hierarchical biomimetic structures with order beyond the nanoscale, and also discuss the future prospects of these supramolecular systems.     

Solvent-Induced Self-Assembly of Highly Hydrophobic Tetra- and Pentaphenylalanine Peptides

Diphenylalanine peptide (FF) self-assembles into ordered structures of notable physical properties. Moreover, the ability of the phenylalanine amino acid or triphenylalanine to assemble into ordered nanostructures had been demonstrated. Herein, we explored the association potential of larger phenylalanine peptides, tetraphenylalanine, and pentaphenylalanine. A major challenge in studying the assembly of these peptides is their lack of solubility in different solvents. Yet, the remarkable capacity of acetic acid to solubilize FF was recently shown. Inspired by this, we examined whether this solvent could also be employed to dissolve these insoluble peptides. By utilizing the solvent-switch methodology, we revealed the self-assembly of tetraphenylalanine and pentaphenylalanine. The peptides were assembled into ordered autofluorescent elongated structures, which were further characterized by electron microscopy and spectroscopy analysis and could be utilized in future technological applications.     

Nano-Segregation and Directed Self-Assembly in the Formation of Functional Liquid Crystals

It is often a question that is asked: “How can you predict from the molecular architecture of a material the structure of the condensed phases it forms, and what properties would you expect the phase to exhibit?” For liquid crystals, knowing how to design materials for particular applications requires precision molecular engineering. In this article we examine how molecular topology and interactions influence phase formation and report on material design.     

Supracolloidal Assemblies as Sacrificial Templates for Porous Silk-Based Biomaterials

Tissues in the body are hierarchically structured composite materials with tissue-specific properties. Urea self-assembles via hydrogen bonding interactions into crystalline supracolloidal assemblies that can be used to impart macroscopic pores to polymer-based tissue scaffolds. In this communication, we explain the solvent interactions governing the solubility of urea and thereby the scope of compatible polymers. We also highlight the role of solvent interactions on the morphology of the resulting supracolloidal crystals. We elucidate the role of polymer-urea interactions on the morphology of the pores in the resulting biomaterials. Finally, we demonstrate that it is possible to use our urea templating methodology to prepare Bombyx mori silk protein-based biomaterials with pores that human dermal fibroblasts respond to by aligning with the long axis of the pores. This methodology has potential for application in a variety of different tissue engineering niches in which cell alignment is observed, including skin, bone, muscle and nerve.     

Complex Adaptable Systems based on Self-Assembling Dendrimers and Dendrons: Toward Dynamic Materials

Self-assembling dendrons are biologically inspired complex systems that can form self-organized periodic arrays in the bulk state. Here we adopt the point of view of Constitutional Dynamic Chemistry (CDC) to discuss the design and properties of self-assembling dendrimers and dendronized structures. Among other objectives, CDC seeks to generate chemical diversity through constitutional dynamics, and to improve the design of dynamic materials using adaptive systems. Can we address these issues with dendrimer chemistry? We will show that generational and co-assembly approaches in the synthesis of self-assembling dendritic systems lead to a remarkable collection of periodic lattices and quasi-periodic arrays. Moreover, in some cases the morphological properties of the resulting supramolecular structures can be tuned by external signals. These dendron-based adaptive systems find applications in various fields such as nano-machines and switches or porous protein mimics.     

Mannose‐Decorated Multicomponent Supramolecular Polymers Trigger Effective Uptake into Antigen‐Presenting Cells

A modular route to prepare functional self‐assembling dendritic peptide amphiphiles decorated with mannosides, to effectively target antigen‐presenting cells, such as macrophages, is reported. The monomeric building blocks were equipped with tetra(ethylene glycol)s (TEGs) or labeled with a Cy3 fluorescent probe. Experiments on the uptake of the multifunctional supramolecular particles into murine macrophages (Mφs) were monitored by confocal microscopy and fluorescence‐activated cell sorting. Mannose‐decorated supramolecular polymers trigger a significantly higher cellular uptake and distribution, relative to TEG carrying bare polymers. No cytotoxicity or negative impact on cytokine production of the treated Mφs was observed, which emphasized their biocompatibility. The modular nature of the multicomponent supramolecular polymer coassembly protocol is a promising platform to develop fully synthetic multifunctional vaccines, for example, in cancer immunotherapy.     

Recent Progress in the Synthesis and Structural Clarification of Thermotropic Cubic Phases

This review article focuses on recent advances and challenges in the field of thermotropic cubic phases of the bicontinuous type (Cub_bi) formed by low molecular mass molecules. In the Cub_bi phases, the constituent molecules self-organize into 3D network structures, although local molecular diffusional motions are preserved to some extent. This review illustrates which types of molecules form such structures, and summarizes the latest developments in structural characterization. Moreover, their phase behaviors, and analogies and differences in comparison with other related systems such as lyotropic liquid crystals and block copolymers are discussed. Finally, potential applications utilizing the dynamically ordered 3D network structures are presented.     

Towards Supramolecular Catalysis with Small Self-assembled Peptides

Self-assembly of small peptides offers unique opportunities for the bottom-up construction of supramolecular catalysts that aim to emulate the efficiency and selectivity of natural enzymes. Small, information-rich, simple molecules based on amino acids can self-organise autonomously into complex systems with emergent catalytic properties. The power of noncovalent interactions can be used to construct supramolecular peptidic tertiary structures. Moreover, specific functional groups present in amino acid side-chains may present either a catalytic activity by themselves or be able to bind cofactors such as metal ions. In this scenario, although relevant progress has been achieved in recent years, promising applications in biomaterials science are foreseen. In this review, we discuss the state-of-the-art of this approach at the interface between supramolecular chemistry and peptide science.     

Self-Assembling Peptides: From Design to Biomedical Applications

Self-assembling peptides could be considered a novel class of agents able to harvest an array of micro/nanostructures that are highly attractive in the biomedical field. By modifying their amino acid composition, it is possible to mime several biological functions; when assembled in micro/nanostructures, they can be used for a variety of purposes such as tissue regeneration and engineering or drug delivery to improve drug release and/or stability and to reduce side effects. Other significant advantages of self-assembled peptides involve their biocompatibility and their ability to efficiently target molecular recognition sites. Due to their intrinsic characteristics, self-assembled peptide micro/nanostructures are capable to load both hydrophobic and hydrophilic drugs, and they are suitable to achieve a triggered drug delivery at disease sites by inserting in their structure’s stimuli-responsive moieties. The focus of this review was to summarize the most recent and significant studies on self-assembled peptides with an emphasis on their application in the biomedical field.     

The Impervious Route to Peptide-Based Dye-Sensitized Solar Cells

Electron transfer through peptide scaffolds has been studied for a long time as a useful and simple approach to investigate the mechanisms of the ubiquitous electron-transfer processes in biology. Here, we review our long-standing work in the field, focused on the study of the electronic conduction properties of hybrid devices based on peptide films immobilized on metal surfaces. In particular, we describe the electrochemical and photoelectrochemical properties of peptide-based self-assembled monolayers chemically linked to gold substrates through a disulfide group. Very recently, this work culminated in the construction of a prototype dye-sensitized solar cell, the photoactive element of which was constituted by a helical oligopeptide functionalized with a near-UV-absorbing chromophore. We also take advantage of the occasion to critically review the state of the art of the field, with suggestions for the issues needing further investigation.     

Supramolecular Architectures of Nucleic Acid/Peptide Hybrids

Supramolecular architectures that are built artificially from biomolecules, such as nucleic acids or peptides, with structural hierarchical orders ranging from the molecular to nano-scales have attracted increased attention in molecular science research fields. The engineering of nanostructures with such biomolecule-based supramolecular architectures could offer an opportunity for the development of biocompatible supramolecular (nano)materials. In this review, we highlighted a variety of supramolecular architectures that were assembled from both nucleic acids and peptides through the non-covalent interactions between them or the covalently conjugated molecular hybrids between them.     

Tunable Supramolecular Chirogenesis in the Self-Assembling of Amphiphilic Porphyrin Triggered by Chiral Amines

Supramolecular chirality is one of the most important issues in different branches of science and technology, as stereoselective molecular recognition, catalysis, and sensors. In this paper, we report on the self-assembly of amphiphilic porphyrin derivatives possessing a chiral information on the periphery of the macrocycle (i.e., D- or L-proline moieties), in the presence of chiral amines as co-solute, such as chiral benzylamine derivatives. The aggregation process, steered by hydrophobic effect, has been studied in aqueous solvent mixtures by combined spectroscopic and topographic techniques. The results obtained pointed out a dramatic effect of these ligands on the morphology and on the supramolecular chirality of the final self-assembled structures. Scanning electron microscopy topography, as well as fluorescence microscopy studies revealed the formation of rod-like structures of micrometric size, different from the fractal structures formerly observed when the self-assembly process is carried out in the absence of chiral amine co-solutes. On the other hand, comparative experiments with an achiral porphyrin analogue strongly suggested that the presence of the prolinate moiety is mandatory for the achievement of the observed highly organized suprastructures. The results obtained would be of importance for unraveling the intimate mechanisms operating in the selection of the homochirality, and for the preparation of sensitive materials for the detection of chiral analytes, with tunable stereoselectivity and morphology.     

超分子自组装及其在高分子合成领域中的应用

超分子自组装是近年来倍受重视的国际前沿课题,它将会极大促进信息、能源、生命、环境和材料科学等学科领域的发展,介绍了基于氢键、π键、配位键、双亲分子4种自组装体系,重点综述了这4种自组装体系在高分子合成领域中的最新进展,最后对超分子自组装的发展趋势做了展望。     

超分子材料研究进展

本文综述了超分子材料的发展概况,并介绍了超分子器件、超分子液晶、超分子生物材料和超分子纳米材料等超分子化技术的研究进展,展望了超分子材料的发展前景及其开发应用潜力。     

Chemistry in Restricted Spaces: Select Photodimerizations in Cages,Cavities, and Capsules

Carrying out chemical transformations under environmentally sustainable conditions has become one of the important current goals of chemistry. In this context, conducting reactions under solvent-free conditions (crystals, zeolites, clay, etc.) and in water has attracted considerable attention. Since most molecules either do not crystallize and or do not dissolve in water, the two approaches are complimentary. To make molecules solubilize in water one needs to employ water-soluble hosts such as micelles, cavitands, and capsules. To achieve selectivity, one should provide a confined environment within which the motions of reactant molecules are restricted to that in free solution. The confined space in which the reaction takes place independent of the host environment could be defined in terms of the “reaction cavity” originally presented by Cohen and Schmidt. In this mini-review, examples of photodimerization of olefins carried out in cavitands such as cucurbiturils, cyclodextrins, calixarenes, and octa acid are presented. Results are discussed in terms of the reaction cavity concept, which is applicable to reactions in both solids and water.     

自组装合成超分子液晶聚合物研究进展

从电荷转移作用、离子相互作用、氢键作用组装、金属配位组装、光化学组装5个方面综述了通过分子自组装合成超分子液晶聚合物的近年来的最新研究成果,并介绍了超分子液晶聚合物的应用及发展前景。     

Peptide-Based Materials That Exploit Metal Coordination

Metal–ion coordination has been widely exploited to control the supramolecular behavior of a variety of building blocks into functional materials. In particular, peptides offer great chemical diversity for metal-binding modes, combined with inherent biocompatibility and biodegradability that make them attractive especially for medicine, sensing, and environmental remediation. The focus of this review is the last 5 years’ progress in this exciting field to conclude with an overview of the future directions that this research area is currently undertaking.