Protein-mimetic peptide nanofibers: Motif design, self-assembly synthesis, and sequence-specific biomedical applications (2023)

Table of Contents
Progress in Polymer Science Abstract Introduction Section snippets Creation and properties of PMP nanofibers Motif design and sequence-specific applications Conclusions and perspectives Acknowledgements References (247) Fabrication of molecular materials using peptide construction motifs Trends Biotechnol Mimicry of bioactive peptides via non-natural, sequence-specific peptidomimetic oligomers Curr Opin Chem Biol Protein aggregation kinetics, mechanism, and curve-fitting: a review of the literature Biochim Biophys Acta Bottom-up synthesis and sensor applications of biomimetic nanostructures Materials Emerging biological materials through molecular self-assembly Biotechnol Adv In situ-forming injectable hydrogels for regenerative medicine Prog Polym Sci Fabrication of graphene-biomacromolecule hybrid materials for tissue engineering application Polym Chem Detection of changes in near-membrane Ca2+ concentration using a novel membrane-associated Ca2+ indicator J Biol Chem Green electrospun pantothenic acid/silk fibroin composite nanofibers: fabrication, characterization and biological activity Colloids Surf B Molecular mechanisms for intrafibrillar collagen mineralization in skeletal tissues Biomaterials RGD and BMP-2 mimetic peptide crosstalk enhances osteogenic commitment of human bone marrow stem cells Acta Biomater Self-assembling peptide amphiphile nanofiber matrices for cell entrapment Acta Biomater ATR-FTIR: A. rejuvenated tool to investigate amyloid proteins Biochim Biophys Acta Analysis of insulin amyloid fibrils by Raman spectroscopy Biophys Chem The extracellular matrix: at the center of it all J Mol Cell Cardiol Bio-inspired in situ crosslinking and mineralization of electrospun collagen scaffolds for bone tissue engineering Biomaterials Elastin-like polypeptides in drug delivery Adv Drug Deliv Rev The effect of a recombinant elastin-mimetic coating of an ePTFE prosthesis on acute thrombogenicity in a baboon arteriovenous shunt Biomaterials Molecular biomimetics: nanotechnology through biology Nat Mater Designing peptide based nanomaterials Chem Soc Rev Functional supramolecular polymers Science Small peptides as potent mimetics of the protein hormone erythropoietin Science Biomimetic self-assembled nanofibers Soft Matter Concepts and progress in the development of peptide mimetics J Med Chem Self-assembly of surfactant-like peptides with variable glycine tails to form nanotubes and nanovesicles Nano Lett Structural and functional features of a collagen-binding matrix protein from the mussel byssus Nat Commun Self-assembling peptide and protein amyloids: from structure to tailored function in nanotechnology Chem Soc Rev Design, fabrication, and biomedical applications of bioinspired peptide-inorganic nanomaterial hybrids J Mater Chem B Self-assembling polymer systems for advanced treatment of cancer and inflammation Prog Polym Sci Designer self-assembling peptide nanofiber biological materials Chem Soc Rev Self-assembly of fibronectin mimetic peptide-amphiphile nanofibers Langmuir Self-assembly of peptides to nanostructures Org Biomol Chem Bioactive supramolecular peptide nanofibers for regenerative medicine Adv Healthc Mater Bioinspired structural materials Nat Mater Catalytic activity of copper ions in the amyloid fibrillation of β-lactoglobulin Soft Matter Role of metal Ions in the self-assembly of the Alzheimer's amyloid-β peptide Inorg Chem Amyloids: not only pathological agents but also ordered nanomaterials Angew Chem Int Ed Engl The self-assembly, aggregation and phase transitions of food protein systems in one, two and three dimensions Rep Prog Phys Fibronectin fibrillogenesis on sulfonated polystyrene surfaces J Biomed Mater Res Cooperative, reversible self-assembly of covalently pre-linked proteins into giant fibrous structures Angew Chem Int Ed Engl Ca2+-induced self-assembly of Bombyx mori silk sericin into a nanofibrous network-like protein matrix for directing controlled nucleation of hydroxylapatite nano-needles J Mater Chem B Self-assembly of ovalbumin into amyloid and non-amyloid fibrils Biomacromolecules Self-assembly of protein-based biomaterials initiated by titania nanotubes Langmuir Self-assembly of protein fibrils into suprafibrillar aggregates: bridging the nano- and mesoscale ACS Nano Beaded nanofibers assembled from double-hydrophobic elastin-like block polypeptides: effects of trifluoroethanol Biopolymers Metal-directed, chemically tunable assembly of one-, two- and three-dimensional crystalline protein arrays Nat Chem Directed growth of silk nanofibrils on graphene and their hybrid nanocomposites ACS Macro Lett Subtle charge balance controls surface-nucleated self-assembly of designed biopolymers ACS Nano Hierarchical structure and nanomechanics of collagen microfibrils from the atomistic scale up Nano Lett Uncovering nanoscale electromechanical heterogeneity in the subfibrillar structure of collagen fibrils responsible for the piezoelectricity of bone ACS Nano Cited by (126) Recent trends in graphene assisted vanadium based nanocomposites for supercapacitor applications Synergism of silver/CEM drug on novel proteinaceous silk fibroin/mesoporous silica based sandwich-layered nanofibrous scaffolds for osteoregenerative applications A review on fabrication methods of nanofibers and a special focus on application of cellulose nanofibers Nanofibrous hemostatic materials: Structural design, fabrication methods, and hemostatic mechanisms Recent progress on hybrid fibrous electromagnetic shields: Key protectors of living species against electromagnetic radiation Real-time fluorescence dynamics in one-step synthesis of gold nanoclusters coupling with peptide motifs Recommended articles (6) Active immunotherapy for TNF-mediated inflammation using self-assembled peptide nanofibers Improving pancreatic islet in vitro functionality and transplantation efficiency by using heparin mimetic peptide nanofiber gels Peptide-coordination self-assembly for the precise design of theranostic nanodrugs Spectroscopic investigation of highly-scattering nanofiber mats during drying and film formation Self-assembled peptide nanofibers on graphene oxide as a novel nanohybrid for biomimetic mineralization of hydroxyapatite Emerging Applications of Supramolecular Peptide Assemblies

Progress in Polymer Science

Volume 80,

May 2018

, Pages 94-124

Author links open overlay panel, , , , ,

Abstract

The design and fabrication of self-assembled peptide nanostructures offer an amazing platform for creating functional nanomaterials for various biomedical applications. Utilizing the mechanical and biological advantages of the protein-mimetic peptide (PMP) system, and combining self-assembled PMP nanofibers with other nanomaterials like nanoparticles, the fabricated PMP-based hybrid fibrous nanostructures can serve as promising candidates for advanced technological applications. In this review, we present the design, synthesis, modification, and fabrication of PMP nanofibers by mimicking the properties and functions of several types of proteins, including extracellular matrix proteins, silk proteins, amyloid proteins, and heparin. The sequence and motif design of PMPs, and the relationships between the design of PMP monomers and the fabrication of functional fibrous biomaterials are introduced and discussed. Furthermore, we summarize a basic classification of various peptide motifs, and provide some instructions for the function-based design of peptide nanostructures, in which some issues on the motif design and function tailoring are discussed. Finally, the recent advances in the PMP nanofiber-based functional nanomaterials in biomineralization, cell culture, tissue regeneration, drug delivery, hemostasis, bioimaging, and biosensors are presented in detail. We believe that this review will be very helpful for researchers to understand the property-specific molecular design, controllable supramolecular self-assembly, and motif-specific applications of both peptides and proteins.

Introduction

Supramolecular self-assembly is an important and effective strategy to form a large and organized bimolecular superstructure, by which biomolecules can achieve their bioactive functions. For example, aptamers can assemble to RNA and DNA, to carry genetic information into chromosomes; amino acids can assemble to secondary peptide structures and then fold into a more complex protein molecule. The natural self-assembly and disassembly of biomolecules develops bioactive macromolecular systems with enormous complexity, able to achieve most of the in vivo functions for organisms. Inspired by the self-assembly of biomolecular building blocks, numerous artificial supramolecular systems have been designed and created over the past few decades [[1], [2], [3], [4]]. It is well known that proteins with high molecular weight, diverse functions, and high complexity are difficult to synthesize and simulate at the molecular level, while peptides possess much more potential for theoretical and experimental investigations of the partial functions of proteins. Thanks to the rapid development of peptide synthesis techniques, it is possible to synthesize peptides with the desired amino acid sequence, expectable bio-properties, and controllable self-assembly ability. Peptides created by mimicking the functions and properties of natural proteins, called protein-mimetic peptides (PMPs) [5,6], have developed into a versatile platform for building multifunctional biocompatible materials.

From the biological point of view, PMPs offer an alternative opportunity to understand and utilize proteins in an indirect way. It is known that the natural proteins organized through long-time evolution and in vivo formation. Therefore, their highly ordered superstructures and attractive functions provide inspirations for designing artificial nanostructures with high biocompatibility and nature-similar mechanical characteristics. Previously, more and more sequences of proteins and their self-assembly properties have been revealed, but an understanding of the inner relations between sequences and functions of amino acids remains a great challenge. PMPs with designed motifs, structures, and functions that relate to the properties of whole proteins may lead to the potential understanding of the inner folding, unfolding, and aggregation mechanisms of proteins, including i) the inner relations between amino acid sequence and protein functions, ii) the relations between sequence and self-assembly formation, and iii) the potential connections between protein aggregation and controlled self-assembly of peptides. On the other hand, the accidental misfolding of proteins and subsequent protein aggregation may be implicated in severe diseases, such as Alzheimer's, Huntington's, Parkinson's, and prion diseases [[7], [8], [9]]. For example, Alzheimer's disease is caused by the aggregation of misfolded proteins into amyloid-β plaques, leading to the formation of protein fibrils and following neurodegenerative disorders [8]. To inhibit the protein fibrillation, numerous studies have been conducted to analyze both amino acid sequences and structures of proteins to understand the protein folding, misfolding, aggregation, and corresponding self-assembly mechanisms [9]. Therefore, studying the controllable self-assembly of PMPs and the formation of PMP nanofibers may significantly contribute to the evolution of understanding the inner mechanisms of protein fibrillation and the rapid development of novel biomedical applications of PMPs.

It is possible to determine some short amino acid sequences that relate to the main functions and properties of proteins by the structural analysis of proteins. When a segment of amino acid sequence is associated with specific functions, the sequence can be defined as a motif. Nature defines many structural and biofunctional motifs through billions of years of evolution, and there are many natural motifs having been observed in natural proteins. One motif may exist in many different proteins containing the same sequence, displaying similar functions. As more and more structures and functions of peptide motifs have been investigated and identified, they have been regarded as potential building blocks for creating peptide-based functional materials. To construct peptide nanofibers and three-dimensional (3D) nanofibrous scaffolds, a peptide monomer often consists of both structural building block(s) and bioactive motif(s). The motif of a peptide determines the occurrence, driving forces (including non-covalent forces like ionic force, hydrogen bond, hydrophobic force, and π-π stacking), and ultimate formation of peptide nanofibers [10]. These driving forces offer a mild and bottom-up approach to fabricate various supramolecular nanostructures.

Previously, a large number of self-assembled peptide superstructures have been reported, including peptide nanofibers, nanotubes, and nanovesicles [11,12]. This review is focussed on the synthesis, self-assembly, and bioapplications of PMPs. So far, the studies of PMPs are mostly focused on the sequence design of PMPs and their self-assembly synthesis of PMP nanofibers with similar functions as those of mimetic proteins, offering versatile solutions for the construction of structure- and function-unique biomaterials. In addition, more functions and properties of a PMP can be obtained by further adding other functional short motifs into the original PMP sequence, and therefore the multifunctional PMP molecule will preserve not only the properties of self-assembly, biocompatibility, and bio-recognition, but also the abilities of binding with other nanomaterials, such as nanoparticles, carbon nanotubes, graphene, and others [13,14].

Among various morphologies of self-assembled peptide nanostructures that have been reported, nanofibrous structures are considered to be the most promising candidates for many applications. Fibrous structures are the most common morphologies in the self-assembly process of peptides, which possess large length-to-diameter ratio, sufficient functional groups, and flexible shape for further fabrication. Hierarchical architectures with self-assembled peptide nanofibers may be constructed via entanglement and non-covalent binding between peptide nanofibers. Such 3D materials would play essential roles in peptide-based nanomaterials, leading to extended applications. Therefore, self-assembled PMP nanofibers are promising building blocks for biomedical applications, such as biomineralization, cell culture, tissue regeneration, drug delivery, homostasis, bioimaging, and biosensors [[15], [16], [17]].

In this review, we aim to summarize the recent advances in the synthesis, modification, self-assembly, and biomedical applications of PMPs. First, we present the design and synthesis of some typical PMPs by mimicking proteins like extracellular matrix (ECM), silk, amyloid-β, and heparin proteins. The sequence and motif design of the PMPs, and the relationships between the design of PMP monomers and the fabrication of functional biomaterials will be discussed. Second, we summarize a basic classification of various peptide motifs, and give relevant information for the design of functional PMPs. In addition, some issues on the motif design will be discussed. Third, recent biomedical applications of PMP nanofibers and nanofiber-based hybrid materials will be demonstrated. In this part, some basic guidelines on the molecular design, synthesis, and fabrication of PMP nanofibers will be provided. Finally, several future perspectives for this emerging field will be given.

Section snippets

Creation and properties of PMP nanofibers

As the most basic biological materials, natural proteins, including collagen, fibrin, silk, and others, play an important role in life science and biomaterial science [18]. However, natural proteins usually have large size, complex chemical composition, and intricate structure, rendering the synthesis and fabrication of protein-based materials at the molecular level a great challenge [19]. In addition, improper temperature or chemical treatment could lead to the denaturation of proteins, making

Motif design and sequence-specific applications

PMPs can be transformed to particular, well-defined nanostructures by mimicking naturally occurring proteins, usually bolstered by the substantial progress in computer simulations [141,142]. Previously, an increasing number of studies have been devoted to understand the relationship between the amino acid sequence of a peptide and its functional properties, as well as folding behavior [143]. Such studies will greatly promote the emergence of new peptides with desired structural, functional, and

Conclusions and perspectives

In summary, we reviewed the synthesis, motif design, self-assembly formation of nanofibers, and various biomedical applications of several types of PMPs. Aiming at different biofunctions and microstructural formation, different motifs were selected and linked by a specific linker. Therein, each part of complete PMP chain must be obtained by solid-phase synthesis. The artificially designed PMPs hold the advantages of controllable multifunction, low toxicity, and high biocompatibility, which are

Acknowledgements

WZ, XY, YL, and ZS gratefully acknowledge the financial supports from the National Natural Science Foundation of China (NSFC, Grant No. 51573013). KDJ gratefully acknowledges the partial financial support of the Deutsche Forschungsgemeinschaft (DFG, Novel functional materials based on self-assembled protein nanofibers; creating and undersdanding nanofibers.) under grants of AOBJ 609403 and PolyTarget (SFB 1278), Project A06. GW thanks for the financial support of the DFG under grant WE 5837/1-1.

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      Improving pancreatic islet in vitro functionality and transplantation efficiency by using heparin mimetic peptide nanofiber gels

      Acta Biomaterialia, Volume 22, 2015, pp. 8-18

      Pancreatic islet transplantation is a promising treatment for type 1 diabetes. However, viability and functionality of the islets after transplantation are limited due to loss of integrity and destruction of blood vessel networks. Thus, it is important to provide a proper mechanically and biologically supportive environment for enhancing both in vitro islet culture and transplantation efficiency. Here, we demonstrate that heparin mimetic peptide amphiphile (HM-PA) nanofibrous network is a promising platform for these purposes. The islets cultured with peptide nanofiber gel containing growth factors exhibited a similar glucose stimulation index as that of the freshly isolated islets even after 7days. After transplantation of islets to STZ-induced diabetic rats, 28day-long monitoring displayed that islets that were transplanted in HM-PA nanofiber gels maintained better blood glucose levels at normal levels compared to the only islet transplantation group. In addition, intraperitoneal glucose tolerance test revealed that animals that were transplanted with islets within peptide gels showed a similar pattern with the healthy control group. Histological assessment showed that islets transplanted within peptide nanofiber gels demonstrated better islet integrity due to increased blood vessel density. This work demonstrates that using the HM-PA nanofiber gel platform enhances the islets function and islet transplantation efficiency both in vitro and in vivo.

    • Research article

      Peptide-coordination self-assembly for the precise design of theranostic nanodrugs

      Coordination Chemistry Reviews, Volume 397, 2019, pp. 14-27

      Peptide-coordination self-assembly demonstrates great potential in the precise design of next-generation theranostic nanodrugs. It has the advantages of high biosafety, versatile system design, easy control over the self-assembled structures, facile incorporation of various functionalities, and greatly enhanced stability of the complex materials as well as their stimuli-responsive assembly and disassembly. All of these merits promote the construction of targeted theranostic systems with highly integrated diagnostic and therapeutic functionalities. This review seeks to provide an up-to-date conclusive observation about the field of peptide-coordination self-assembly for theranostic applications to guide related research. It covers the general principles of peptide-coordination self-assembly for producing structures with controlled morphologies and properties, the strategies for constructing peptide/metal hybrid materials for diagnostic and therapeutic aims, and, more specifically, the strategies and design rules for integrating various functionalities into a single platform for theranostics.

    • Research article

      Spectroscopic investigation of highly-scattering nanofiber mats during drying and film formation

      Optik, Volume 208, 2020, Article 164081

      Electrospun nanofiber mats show a very high surface-to-volume ratio as well as good mechanical properties and are thus typically used as filters or wound dressings, for drug delivery or as catalysts. Their optical properties, however, are only scarcely investigated. Due to the fine fibers with typical diameters of a few hundred nanometers, they tend to scattering visible light strongly. When wetted, however, they can become nearly invisible due to index-matching with the solvent and benefiting from the low thickness of the mats of usually only few microns. Here we report on polyacrylonitrile nanofiber mats, electrospun solely or blended with biopolymers, ceramics and other materials to modify their morphological and optical properties. Spectroscopic investigations of wetted nanofiber mats revealed different drying processes for different nanofiber morphologies and materials. On the other hand, some nanofiber mats were dissolved and the nano-mat forming process was evaluated spectroscopically, underlining the significant difference in the optical properties of nanofiber mats and nano-membranes of identical areal weights. With that we show the capability of the nanofiber mats for reversible transmission as well as permanent transmission tuning.

    • Research article

      Self-assembled peptide nanofibers on graphene oxide as a novel nanohybrid for biomimetic mineralization of hydroxyapatite

      Carbon, Volume 89, 2015, pp. 20-30

      In this study, self-assembled peptide nanofibers (PNFs) were firstly created with a specially designed peptide molecule. Graphene oxide (GO) nanosheet, as a two-dimensional scaffold, was then modified with the prepared PNFs to fabricate a new type of GO–PNF nanohybrid, which was further utilized as a template for biomimetic mineralization. The produced GO–PNF nanohybrid and its minerals were characterized by atomic force microscopy, scanning electron microscopy, Fourier transform infrared spectroscopy, X-ray diffraction, Raman spectroscopy, and thermogravimetric analysis. The obtained results indicate that the created GO–PNF nanohybrid facilitates the nucleation and growth of hydroxyapatite (HA) crystals. The created PNFs promote the formation of HA nanocrystals along the axis of PNFs within short-term incubation and the GO nanosheet mediates the formation of HA microsphere after long-term mineralization. The effects of the produced GO–PNF nanohybrid and biomimetic minerals (GO–PNF–HA) on the adhesion and proliferation of L-929 cells and MC3T3-E1 cells were further investigated. The cell culture result indicates that the produced GO–PNF–HA minerals have good biocompatibility and can enhance the proliferation ability of the studied cells. We believe this novel biocompatible nanohybrid will show great potentials in tissue engineering.

    • Research article

      Emerging Applications of Supramolecular Peptide Assemblies

      Trends in Chemistry, Volume 2, Issue 1, 2020, pp. 71-83

      Supramolecular peptide assemblies not only provide molecular insight into understanding and mimicking the fundamental features of the self-assembly of biological molecules, but also promise many important applications. This review discusses representative examples of supramolecular assemblies of peptides or peptide derivatives and highlights the emerging applications of these materials, including tissue engineering, molecular imaging, and cancer therapeutics. These results underscore the tremendous promise of supramolecular peptide assemblies as an emerging interdisciplinary research branch at the interface of chemistry and biological science.

    1

    These authors contribute equally to this work.

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