Constructing biomaterials using self-assembling peptide building blocks

Molecular self-assembly is ubiquitous in nature and has recently emerged as a new bottom-up approach in constructing biomaterials. Synthetic peptides assemble through specific molecular recognition and form diverse nanostructures. The resulting versatile peptide self-assemblies may be used in a wide range of biological and medical applications. Examples of two self-assembling peptide systems are presented and techniques for self-assembly control are discussed.     

Engineering protein and peptide building blocks for nanotechnology

The tremendous diversity in the structure and function of proteins has stimulated intense interest in using them for nanotechnology applications. In this review, we discuss recent developments in the engineering of proteins and peptides for the design and construction of functional and structural elements of nanodevices. We begin with a short discussion highlighting the differences between chemical and biological synthesis of proteins and peptides. Subsequently, we review recent applications of proteins and peptides as molecular motors, transducers, biosensors, and structural elements of nanodevices. We supplement this review with highlights of our own work in the areas of peptide-based transducers for stand-alone and intra-molecular applications. This is followed by a short discussion of nanotechnology safety issues, and how proteins and peptides may enable the development of biocompatible nanomaterials. The future outlook for protein and peptide-based nanomaterials is then discussed, with an eye toward the significant impact of improved computational techniques on the field.     

Silver-doped self-assembling di-phenylalanine hydrogels as wound dressing biomaterials

Chronic and acute wounds can be quickly contaminated and infected by microorganisms such as bacteria, multi-resistant organisms or fungi. The introduction of silver as anti-microbial agent into wound management has widely been demonstrated to be effective and contribute to wound healing. As a consequence, many approaches and different materials have been employed to synthesize antibacterial silver-hydrogels. In this work the introduction of silver particles into the fibrillar structure of self-assembling aromatic di-phenylalanine derivatives modified with aromatic groups such as 9-fluorenylmethoxycarbonyl is proposed to produce antibacterial wound dressings. Hydrogels doped with increasing amounts of silver were tested and adopted to modify flax textiles. The influence of silver on the structure of hydrogels was studied using light and confocal microscopy, while SEM–EDX allowed the characterization of the hydrogel coating on the surface of the textile substrates as well as the identification and distribution of silver nanoparticles. The antibacterial potential of the treated flax was demonstrated through microbiological tests on Staphylococcus aureus. The combination of the physico-chemical and anti-bacterial properties, together with the ease of preparation of these biomaterials, fulfils the requirement of clinically-effective wound dressings.     

Construction of helical nanofibers from self-assembling pseudopeptide building blocks: modulating the handedness and breaking the helicity

Helical nanofibers are successfully constructed from suitable self-assembling pseudopeptide-based molecular building blocks. The handedness of these nanofibers can be reversed by using mirror-imaged pseudopeptide-based building blocks. Straight nanofibers are also constructed by modulating the molecular and supramolecular structures by the proper choice of the stereochemical nature of the molecular scaffolds. This study demonstrates that molecular structure and chirality are not the only determining factors for tuning the morphology and chirality of nanostructures; the nature of the supramolecular structures formed from the corresponding molecular scaffolds also plays a key role in dictating the shape and chirality of nanostructures. Helical nanofibers are suitable templates for fabricating dipeptide-capped gold nanoparticles, indicating a possible use of these nanofibers in the construction of arrays of gold nanoparticles.     

DNA as nanoscale building blocks

The use of DNA as programmable building blocks to achieve highly-definable nanostructures, termed as DNA nanotechnology, has offered great opportunities to control matter at a very small scale. Fast growing researches along this direction has led to the emergence of several significant branches of DNA nanotechnology. This review intends to summarize the recent developments in this area. Several topics will be discussed with a focus on the works from the authors' group, including (1) DNA self-assembly and DNA-directed self-assembly, (2) DNA nanomachines, (3) DNA-based electronics, (4) DNA assisted nanofabrications, and (5) DNA computations.     

Systematic studies of a self-assembling peptide nanofiber scaffold with other scaffolds

A designer self-assembling peptide nanofiber scaffold has been systematically studied with 10 commonly used scaffolds in a several week study using neural stem cells (NSC), a potential therapeutic source for cellular transplantations in nervous system injuries. These cells not only provide a good in vitro model for the development and regeneration of the nervous system, but may also be helpful in testing for cytotoxicity, cellular adhesion, and differentiation properties of biological and synthetic scaffolds used in medical practices. We tested the self-assembling peptide nanofiber scaffold with the most commonly used scaffolds for tissue engineering and regenerative medicine including PLLA, PLGA, PCLA, collagen I, collagen IV, and Matrigel. Additionally, each scaffold was coated with laminin in order to evaluate the utility of this surface treatment. Each scaffold was evaluated by measuring cell viability, differentiation and maturation of the differentiated stem cell progeny (i.e. progenitor cells, astrocytes, oligodendrocytes, and neurons) over 4 weeks. The optimal scaffold should show high numbers of living and differentiated cells. In addition, it was demonstrated that the laminin surface treatment is capable of improving the overall scaffold performance. The designer self-assembling peptide RADA16 nanofiber scaffold represents a new class of biologically inspired material. The well-defined molecular structure with considerable potential for further functionalization and slow drug delivery makes the designer peptide scaffolds a very attractive class of biological material for a number of applications. The peptide nanofiber scaffold is comparable with the clinically approved synthetic scaffolds. The peptide scaffolds are not only pure, but also have the potential to be further designed at the molecular level, thus they promise to be useful for cell adhesion and differentiation studies as well as for future biomedical and clinical studies.     

Tailor made synthesis of Q-TiO2 powder by using quantum dots as building blocks

A simple synthetic procedure based on ultrasonic spray pyrolysis and usage of TiO₂ quantum dots as building blocks leads to the formation of submicronic TiO₂ spheres which preserved optical and catalytic properties of the constituting elements. The methodology is not limited to semiconductor quantum dots, but provides general procedures for the rational design of novel and potentially useful composite materials.     

DNA-nanoparticle superlattices formed from anisotropic building blocks

Directional bonding interactions in solid-state atomic lattices dictate the unique symmetries of atomic crystals, resulting in a diverse and complex assortment of three-dimensional structures that exhibit a wide variety of material properties. Methods to create analogous nanoparticle superlattices are beginning to be realized, but the concept of anisotropy is still largely underdeveloped in most particle assembly schemes. Some examples provide interesting methods to take advantage of anisotropic effects, but most are able to make only small clusters or lattices that are limited in crystallinity and especially in lattice parameter programmability. Anisotropic nanoparticles can be used to impart directional bonding interactions on the nanoscale, both through face-selective functionalization of the particle with recognition elements to introduce the concept of valency, and through anisotropic interactions resulting from particle shape. In this work, we examine the concept of inherent shape-directed crystallization in the context of DNA-mediated nanoparticle assembly. Importantly, we show how the anisotropy of these particles can be used to synthesize one-, two- and three-dimensional structures that cannot be made through the assembly of spherical particles.     

EPOS, building blocks for search strategies

The article describes the EPOS database of the EPO, which includes synomyms and all expressions that can be used in text dealing with a particular subject. Examples are given of use of the database in searching.     

Designer self-assembling peptide scaffold stimulates pre-osteoblast attachment, spreading and proliferation

A new peptide scaffold was made by mixing pure RADA16 (Ac-RADARADARADARADA-CONH2) and designer peptide RGDA16 (Ac-RADARGDARADARGDA-CONH2) solutions, and investigate any effect on attachment, spreading and proliferation of pre-osteoblast (MC3T3-E1). The peptides, RADA16 and RGDA16, were custom-synthesized. They were solubilized in deionized water at a concentration of 10 mg/ml (1% w/v), the RGDA16 peptide solution was mixed 1:1 with RADA16 solution and a new peptide solution RGDAmix was produced. The RGDAmix and RADA16 solution were directly loaded in 96-well plates and cover slips, and two different peptide scaffolds were formed with the addition of maintenance medium (α-MEM) in several minutes. About 1.0 × 10⁴ MC3T3-E1 cells were seeded on each hydrogel scaffold, and then the cell morphological changes were observed using a fluorescence microscope at 1 h, 3 h and 24 h timepoint, respectively. Cell attachment was evaluated 1 h, 3 h and 24 h after cell seeding and cell proliferation was determined 4d, 7d and 14d after cell seeding. The RGDAmix scaffold significantly promoted the initial cell attachment compared with the RADA16 scaffold. MC3T3-E1 cells adhered and spread well on both scaffolds, however, cells spread better on the RGDAmix scaffold than on the RADA16 scaffold. Cell proliferation was greatly stimulated when cultured on RGDAmix scaffold. The RGD sequence contained peptide scaffold RGDAmix significantly enhances MC3T3-E1 cells attachment, spreading and proliferation.     

A neurotrophic peptide-functionalized self-assembling peptide nanofiber hydrogel enhances rat sciatic nerve regeneration

Nerve guidance conduit (NGC) is a potential alternative to autologous nerve for peripheral nerve regeneration. A promising therapeutic strategy is to modify the nerve guidance conduit intraluminal microenvironment using physical and/or chemical guidance cues. In this study, a neurotrophic peptide-functionalized self-assembling peptide nanofiber hydrogel that could promote PC12 cell adhesion, proliferation, and neuronal differentiation in vitro was prefilled in the lumen of a hollow chitosan tube (hCST) to accelerate axonal regeneration in a rat sciatic nerve defect model. The functionalized self-assembling peptide was developed by introducing a neurotrophic peptide (RGI, RGIDKRHWNSQ) derived from brain-derived neurotrophic factor (BDNF) to the C-terminus of the self-assembling peptide RADA16-I (Ac-(RADA)₄-CONH₂). Morphological, histological, electrophysiological, and functional analyses demonstrated that the RGI-functionalized, self-assembling, peptide nanofiber hydrogel RAD/RGI could produce a neurotrophic microenvironment that markedly improved axonal regeneration with enhanced re-myelination and motor functional recovery.

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Organic molecular magnets-the search for stable building blocks

The greatest problem in creating organic molecular magnets seems to be to find systems in which there is a strong exchange interaction but which are also chemically and thermally stable. This paper discusses one possible solution to this problem, the use of strain protection, and the synthesis of stable strain-protected pi biradical, trioxytriangulene. This is the first representative of a new, unexplored family of pi biradicals, the non-Kekulé polynuclear aromatics.     

Organic molecular magnets-the search for stable building blocks

The greatest problem in creating organic molecular magnets seems to be to find systems in which there is a strong exchange interaction but which are also chemically and thermally stable. This paper discusses one possible solution to this problem, the use of ‘strain protection’, and the synthesis of stable strain-protected pi biradical, trioxytriangulene. This is the first representative of a new, unexplored family of pi biradicals, the non-Kekulé polynuclear aromatics.     

Nano-architectures by covalent assembly of molecular building blocks

The construction of electronic devices from single molecular building blocks, which possess certain functions such as switching or rectifying and are connected by atomic-scale wires on a supporting surface, is an essential goal of molecular electronics. A key challenge is the controlled assembly of molecules into desired architectures by strong, that is, covalent, intermolecular connections, enabling efficient electron transport between the molecules and providing high stability. However, no molecular networks on surfaces 'locked' by covalent interactions have been reported so far. Here, we show that such covalently bound molecular nanostructures can be formed on a gold surface upon thermal activation of porphyrin building blocks and their subsequent chemical reaction at predefined connection points. We demonstrate that the topology of these nanostructures can be precisely engineered by controlling the chemical structure of the building blocks. Our results represent a versatile route for future bottom-up construction of sophisticated electronic circuits and devices, based on individual functionalized molecules.     

Novel bioinorganic nanostructures based on mesolamellar intercalation or single-molecule wrapping of DNA using organoclay building blocks

Nanosheets or nanoclusters of aminopropyl-functionalized magnesium phyllosilicate (AMP) were prepared in water by exfoliation and used as structural building blocks for the preparation of DNA-based hybrid nanostructures in the form of ordered mesolamellar nanocomposites or highly elongated nanowires, respectively. The former consisted of alternating layers of single sheets of AMP interspaced with intercalated monolayers of intact double-stranded DNA molecules of relatively short length ( approximately 700 base pairs) that were accessible to small molecules such as ethidium bromide. In contrast, the nanowires comprised isolated micrometer-long molecules of lambda-DNA or plasmid DNA that were sheathed in an ultrathin organoclay layer and which were either protected from or remained accessible to endonuclease-mediated clipping depending on the extent of biomolecule wrapping. Both types of hybrid nanostructures showed a marked increase in the DNA melting (denaturation) temperature, indicating significant thermal stabilization of the confined biomolecules. Our results suggest that nanoscale building blocks derived from organically modified inorganic clays could be useful agents for enhancing the chemical, thermal, and mechanical stability of isolated molecules or ensembles of DNA. Such constructs should have increased potential as functional components in bionanotechnology and nonviral gene transfection.     

Hyperbolic reflections as fundamental building blocks for multilayer optics

We re-elaborate on the basic properties of lossless multilayers by using bilinear transformations. We study some interesting properties of the multilayer transfer function in the unit disk, showing that hyperbolic geometry turns out to be an essential tool for understanding multilayer action. We use a simple trace criterion to separate multilayers into three classes that represent rotations, translations, or parallel displacements. Moreover, we show that these three actions can be decomposed as a product of two reflections in hyperbolic lines. Therefore, we conclude that hyperbolic reflections can be considered as the basic pieces for a deeper understanding of multilayer optics.     

Transformable functional nanoscale building blocks with wafer-scale silicon nanowires

Through the fusion of electrostatics and mechanical dynamics, we demonstrate a transformable silicon nanowire (SiNW) field effect transistor (FET) through a wafer-scale top-down approach. By felicitously taking advantage of the proposed electrostatic SiNW-FET with mechanically movable SiNWs, all essential logic gates, including address decoders, can be monolithically integrated into a single device. The unification of various functional devices, such as pn-diodes, FETs, logic gates, and address decoders, can therefore eliminate the complex fabrication issues associated with nanoscale integration. These results represent a step toward the creation of multifunctional and flexible nanoelectronics.