Peptide-based Gels Research Articles

Preparation of Peptide-Based Magnetogels for Removing Organic Dyes from Water.

Water pollution by organic dyes represents a major health and environmental issue. Despite the fact that peptide-based hydrogels are considered to be optimal absorbents for removing such contaminants, hydrogel systems often suffer from a lack of mechanical stability and complex recovery. Recently, we developed an enzymatic approach for the preparation of a new peptide-based magnetogel containing polyacrylic acid-modified γ-Fe2O3 nanoparticles (γ-Fe2O3NPs) that showed the promising ability to remove cationic metal ions from aqueous phases. In the present work, we tested the ability of the magnetogel formulation to remove three model organic dyes: methyl orange, methylene blue, and rhodamine 6G. Three different hydrogel-based systems were studied, including: (1) Fmoc-Phe3 hydrogel; (2) γ-Fe2O3NPs dispersed in the peptide-based gel (Fe2O3NPs@gel); and (3) Fe2O3NPs@gel with the application of a magnetic field. The removal efficiencies of such adsorbents were evaluated using two different experimental set-ups, by placing the hydrogel sample inside cuvettes or, alternatively, by placing them inside syringes. The obtained peptide magnetogel formulation could represent a valuable and environmentally friendly alternative to currently employed adsorbents.

Stabilization of a Photoradiated Naphthalene Diimide-Based Organic Radical Anion Inside a Peptide-Based Gel Matrix with an Improvement of Optoelectronic Properties.

An amino acid-conjugated naphthalene diimide (NDI)-based highly red fluorescent radical anion has been found in a water medium under the photoradiated condition. This molecule has failed to form the radical anion in the monomeric state; however, the J aggregation in the aqueous medium has ensured the formation of radical anion in the ambient condition after the irradiation of both sunlight and UV light exposure. Electron paramagnetic resonance (EPR) studies clearly suggest the formation of radical anions. Herein, the stability of the radical anion in the aqueous medium is only a few minutes as a small amount of shaking is enough to quench the radical anion in the solution state. Furthermore, the incorporation of this molecule into a peptide-based hydrogel matrix and the consequent photoirradiation have not only helped to develop radical anion in the gel matrix but also increased the enormous stability of the radical anion inside the hydrogel matrix even for 30 days. It is envisaged that the formation of the radical anion within the gel matrix prevents the free movement of the NDI molecules and restricts the diffusion of molecular oxygen in the system, which leads to the stability of the radical anions in the gel. Moreover, the stability of the radical anion within the gel has helped to enhance the conductivity of the hybrid gel to a great extent. Interestingly, the radical anion-containing hybrid hydrogel has shown a potential photoswitching property.

Enhancing the stability of natural anthocyanins against environmental stressors through encapsulation with synthetic peptide-based gels

The instability of anthocyanin to environmental stressors severely limits its applications as a natural bioactive pigment. To overcome these limitations, this proof-of-concept study utilizes the high biocompatibility of peptide molecules and the unique gel microstructure to develop innovative peptide-based gels. Characterization of the gels was conducted through AFM, SEM, rheological analysis, and CD spectrum. These analyses confirmed the fibrous mesh structure and impressive mechanical strength of the peptide-based gels. The cytotoxicity evaluation using MTT and hemolysis analysis showed high biocompatibility. Encapsulation efficiency analysis and fluorescence microscopy images demonstrated successful and efficient encapsulation of anthocyanins in all four peptide-based gels, with uniform distribution. Moreover, systematic investigations were conducted to assess the impact of peptide-based gels on the stability of natural anthocyanins under environmental stressors such as temperature, pH variations, and exposure to metal ions. Notably, the results revealed a significant enhancement in stability, including improved long-term storage and antioxidant activity. In conclusion, this study successfully developed four novel peptide-based gels that effectively protect natural anthocyanins from environmental stressors, highlighting their potential in various fields such as food and biology.

Engineering the pentapeptide gelation in ethanol by a tiny side-chain difference

Peptide-based gels hold promise for applications in fields ranging from material development to biomedical engineering. However, challenge remains in controlling the assembly of peptides owing to their structure complexity and formation pathways. Here, we report the gelation of four pentapeptides that are slightly different in the side chains of the molecules in ethanol. Results indicated that ECAFF, ECAYF and ECGFF formed ethanol gels, while a transparent solution was obtained by ECGYF. A high storage modulus of ECAFF hydrogel could be up to ∼104 Pa, and such a gel was composed of tightly entangled fiber bundles with more β-sheet secondary structures. We proposed that removing a hydroxyl group from the tyrosine in the pentapeptides enhanced the π-π stacking interactions between the peptides, thus increased the self-assemble tendency into fibrils. In addition, we suggest that a methyl group on the alanine in the peptide sequence play a positively collaborative role in the gelation of peptides compared with glycine. The findings may shed light on devising the peptide gels with desired properties.

Tuning Peptide-Based Hydrogels: Co-Assembly with Composites Driving the Highway to Technological Applications.

Self-assembled peptide-based gels provide several advantages for technological applications. Recently, the co-assembly of gelators has been a strategy to modulate and tune gel properties and even implement stimuli-responsiveness. However, it still comprises limitations regarding the required library of compounds and outcoming properties. Hence, efforts have been made to combine peptide-based gels and (in)organic composites (e.g., magnetic nanoparticles, metal nanoparticles, liposomes, graphene, silica, clay, titanium dioxide, cadmium sulfide) to endow stimuli-responsive materials and achieve suitable properties in several fields ranging from optoelectronics to biomedical. Herein, we discuss the recent developments with composite peptide-based gels including the fabrication, tunability of gels' properties, and challenges on (bio)technological applications.

Tuning of the Supramolecular Helicity of Peptide-Based Gel Nanofibers.

Helical supramolecular architectures play important structural and functional roles in biological systems. The helicity of synthetic molecules can be tuned mainly by the chiral manipulation of the system. However, tuning of helicity by the achiral unit of the molecules is less studied. In this work, the helicity of naphthalimide-capped peptide-based gel nanofibers is tuned by the alteration of methylene units present in the achiral amino acid. The inversion of supramolecular helicity has been extensively studied by CD spectroscopy and morphological analysis. The density functional theory (DFT) study indicates that methylene spacers influence the orientation of π-π stacking interactions of naphthalimide units in the self-assembled structure that regulates the helicity. This work illustrates a new approach to tuning the supramolecular chirality of self-assembled biomaterials.

Plasmonic lipogels: driving co-assembly of composites with peptide-based gels for controlled drug release.

Supramolecular short peptide-based gels are promising materials for the controlled release of drugs (e.g. chemotherapeutic drugs) owing to the biocompatibility and similarity to cell matrix. However, the drug encapsulation and control over its release, mainly the hydrophilic drugs, can be a cumbersome task. This can be overcome through encapsulation/compartmentalization of drugs in liposomes, which can also enable spatiotemporal control and enhanced drug release through a trigger, such as photothermia. Having this in mind, we explored the assembly of silica-coated gold nanoparticles and liposomes (storage units) with dehydropeptide-based hydrogels as a proof-of-concept to afford peptide-based NIR light-responsive lipogels. Several liposomes compositions were assessed that displayed influence on the final assembly properties by combining with silica-coated gold nanorods (∼106 nm). Gold nanospheres (∼11 nm) were used to study the preparation method, which revealed the importance of initially combine liposomes with nanoparticles and then the gelator solution to achieve a closer proximity of the nanoparticles to the liposomes. The control over a hydrophilic model drug, 5(6)-carboxyfluorescein, was only achieved by its encapsulation in liposomes, in which the presence of silica-coated nanorods further enabled the use of photothermia to induce the liposomes phase transition and stimulate the drug release. Further, both composites, the liposomes and silica-coated gold nanorods, induced a lower elastic modulus, but also provided an enhanced gelation kinetics. Hereby, this work advances fabrication strategies for the development of short peptide-based hydrogels towards on-demand, sustained and controlled release of hydrophilic drugs through photothermia under NIR light irradiation.

Dopamine Self-Polymerization as a Simple and Powerful Tool to Modulate the Viscoelastic Mechanical Properties of Peptide-Based Gels.

Dopamine is a small versatile molecule used for various biotechnological and biomedical applications. This neurotransmitter, in addition to its biological role, can undergo oxidative self-polymerization to yield polydopamine, a robust universal coating material. Herein, we harness dopamine self-polymerization to modulate the viscoelastic mechanical properties of peptide-based gels, expanding their ever-growing application potential. By combining rapid peptide assembly with slower dopamine auto-polymerization, a double network gel is formed, where the fibrillar peptide gel network serves as a scaffold for polydopamine deposition, allowing polydopamine to interpenetrate the gel network as well as establishing crosslinks within the matrix. We have shown that triggering the assembly of a lysine-rich peptide gelator in the presence of dopamine can increase the mechanical rigidity of the resultant gel by a factor of 90 in some cases, while retaining the gel’s shear thin-recovery behavior. We further investigate how factors such as polymerization time, dopamine concentration and peptide concentration alter the mechanical properties of the resultant gel. The hybrid peptide–dopamine gel systems were characterized using rheological measurements, circular dichroism spectroscopy and transmission electron microscopy. Overall, triggering peptide gelation in the presence of dopamine represents a simple yet powerful approach to modulate the viscoelastic mechanical properties of peptide-based gels.

Utilizing Frémy's Salt to Increase the Mechanical Rigidity of Supramolecular Peptide-Based Gel Networks.

Peptide-based supramolecular gels are an important class of biomaterials that can be used for biomedical applications ranging from drug delivery to tissue engineering. Methodology that allows one to readily modulate the mechanical properties of these gels will allow yet even a broader range of applications. Frémy's salt is an inorganic salt and long-lived free radical that is known to oxidize phenols. Herein, we show that Frémy's salt can be used to dramatically increase the mechanical rigidity of hydrogels formed by tyrosine-containing self-assembling β-hairpin peptides. When Frémy's salt is added to pre-formed gels, it converts tyrosine residues to o-quinones that can subsequently react with amines present within the lysine side chains of the assembled peptide. This results in the installation of chemical crosslinks that reinforce the gel matrix. We characterized the unoxidized and oxidized gel systems using UV-Vis, transmission electron microscopy and rheological measurements and show that Frémy's salt increases the gel rigidity by nearly one order of magnitude, while retaining the gel's shear-thin/recovery behavior. Thus, Frémy's salt represents an on-demand method to modulate the mechanical rigidity of peptide-based self-assembled gels.

Peptide-Based Gel in Environmental Remediation: Removal of Toxic Organic Dyes and Hazardous Pb2+ and Cd2+ Ions from Wastewater and Oil Spill Recovery.

A dipeptide-based synthetic amphiphile bearing a myristyl chain has been found to form hydrogels in the pH range 6.9-8.5 and organogels in various organic solvents including petroleum ether, diesel, kerosene, and petrol. These organogels and hydrogels have been thoroughly studied and characterized by different techniques including high-resolution transmission electron microscopy, X-ray diffraction, Fourier-transform infrared spectroscopy, and rheology. It has been found that the xerogel obtained from the peptide gelator can trap various toxic organic dyes from wastewater efficiently. Moreover, the hydrogel has been used to remove toxic heavy metal ions Pb2+ and Cd2+ from wastewater. Dye adsorption kinetics has been studied, and it has been fitted by using the Freundlich isotherm equation. Interestingly, the gelator amphiphilic peptide gels fuel oil, kerosene, diesel, and petrol in a biphasic mixture of salt water and oil within a few seconds. This indicates that these gels not only may find application in oil spill recovery but also can be used to remove toxic organic dyes and hazardous toxic metal ions from wastewater. Moreover, the gelator can be recycled several times without significant loss of activity, suggesting the sustainability of this new gelator. This holds future promise for environmental remediation by using peptide-based gelators.

Role of Thermolysin in Catalytic-Controlled Self-Assembly of Fmoc-Dipeptides

In recent years, short peptide self-assembled materials, prepared under the control of the thermolysin catalyst, have been investigated extensively and shown to acquire various morphologies and fun...

Water-Alcohol Bigels from Fatty Acylated Dipeptides.

Peptide-based gels are emerging as an interesting class of biocompatible soft materials. 9-Fluorenylmethoxycarbonyl-protected amino acids and short peptides have gained considerable attention as promising gelators. Peptide amphiphiles, wherein an alkyl chain is appended to a polar peptidic moiety, are another important class of peptide-based gelators. Here, we report the alcohol/water bigels formed by the rather simple fatty acylated dipeptides wherein the peptidic moiety is made up of hydrophobic amino acids, viz., Val, Ile, and Leu. Lauroyl, myristoyl, and palmitoyl were investigated as the N-terminal fatty acyl groups. None of the lauroylated peptides caused gelation of methanol/water and ethanol/water mixtures up to 2 wt % peptide concentration. Eight out of the 27 peptides resulted in distinct bigels. The gels are composed of fibrous aggregates as characterized by electron microscopy. Infrared spectroscopy suggests the β-sheet conformation of the peptidic region in the gels. Using the Ma-IV ethanol/water bigel as the representative gel, entrapment and steady release of the anticancer drug docetaxel are demonstrated. Such bigels from rather simple amphipathic peptides that are easily synthesized and purified through solvent extraction could be attractive gelator candidates with potential application in drug delivery.

Self-Assembling Peptide-Based Hydrogel: Regulation of Mechanical Stiffness and Thermal Stability and 3D Cell Culture of Fibroblasts.

A histidine-containing peptide-based amphiphile (P1) forms a transparent hydrogel within a pH range of 5.5 to 8.5 in phosphate buffer solution. Interestingly, thermal stability and mechanical stiffness are modulated by incorporating different types of dicarboxylic acids into the hydrogels. Inclusion of succinic acid with the molar ratio 2:1 (peptide:dicarboxylic acid) yields improved properties compared to the other tested dicarboxylic acids such as oxalic, glutaric and octanedioic acids. Transmission electron microscopic (TEM) images show the assembly of nanospheres is responsible for the hydrogel obtained from the assembly of native peptide. However, a morphological transformation takes place from nanosphere to nanofibers, when the peptide gels with succinic acid. XRD and FT-IR studies reveal interactions between peptide amphiphiles and the acids are responsible for the formation of a two-component hydrogel. Gel stiffness is enhanced considerably upon the addition of succinic acid to P1 with a 1:2 molar ratio. The two-component gel consisting of peptide and succinic acid has been successfully used for three-dimensional cell culture using mouse fibroblast cell line (NIH-3T3). This indicates future promise for the application of such peptide-based gels as tunable biomaterials in cell culture and regenerative medicine.

Coassembly of Short Peptide and Polyoxometalate into Complex Coacervate Adapted for pH and Metal Ion-Triggered Underwater Adhesion.

The fabrication of peptide assemblies to mimic the functions of natural proteins represents an intriguing aim in the fields of soft materials. Herein, we present a kind of novel peptide-based adhesive coacervate for the exploration of the environment-responsive underwater adhesion. Adhesive coacervates are designed and synthesized by self-assembled condensation of a tripeptide and polyoxometalates in aqueous solution. Rheological measurements demonstrate that the adhesive coacervates exhibit shear thinning behavior, which allows them to be conveniently delivered for interfacial spreading through a narrow gauge syringe without high pressure. The complex coacervates are susceptible to pH and metal ions, resulting in the occurrence of a phase transition from the fluid phase to the gel state. Scanning electron microscopy demonstrates that the microscale structures of the gel-like phases are composed of interconnected three-dimensional porous networks. The rheological study reveals that the gel-like assemblies exhibited mechanical stiffness and self-healing properties. Interestingly, the gel-like samples show the capacity to adhere to various wet solid substrates under the waterline. The adhesion strength of the peptide-based gel is quantified by lap shear mechanical analysis. The fluid coacervate is further exploited in the preparation of "on-site" injectable underwater adhesives triggered by environmental factors. This finding is exciting and serves to expand our capability for the fabrication of peptide-based underwater adhesives in a controllable way.

Supramolecular Assembly of Peptide and Metallopeptide Gelators and Their Stimuli-Responsive Properties in Biomedical Applications.

Supramolecular gels are a fascinating class of soft materials that have attracted significant attention in recent years. They are composed of small molecule gelators that assemble into supramolecular network structures. The resulting space is filled with solvent. Some gel materials are able to respond to various stimuli making them attractive drug delivery vehicles and as matrices for tissue regeneration. Peptide-based gel materials are particularly attractive as they possess numerous advantages including biocompatibility and biodegradability. Stimuli-responsive peptides that alter properties as a function of pH, redox, temperature, and enzymes offer the potential to create materials with tunable characteristics. In addition, the ability of metal ions to improve the strength of gelation or act as a scaffold has become an interesting approach to develop dynamic peptide gel materials. In this review, the stimuli-responsive properties (pH, redox, temperature, and enzyme responsive properties), as well as the biocompatible/-degradable nature of the peptide gelators are highlighted. In addition, metal ions are discussed as a stimulus to enhance peptide gelation and a number of potential applications of these peptide gelators are provided with an outlook on future directions.

Modulating Supramolecular Peptide Hydrogel Viscoelasticity Using Biomolecular Recognition.

Self-assembled peptide-based hydrogels are emerging materials that have been exploited for wound healing, drug delivery, tissue engineering, and other applications. In comparison to synthetic polymer hydrogels, supramolecular peptide-based gels have advantages in biocompatibility, biodegradability, and ease of synthesis and modification. Modification of the emergent viscoelasticity of peptide hydrogels in a stimulus responsive fashion is a longstanding goal in the development of next-generation materials. In an effort to selectively modulate hydrogel viscoelasticity, we report herein a method to enhance the elasticity of β-sheet peptide hydrogels using specific molecular recognition events between functionalized hydrogel fibrils and biomolecules. Two distinct biomolecular recognition strategies are demonstrated: oligonucleotide Watson-Crick duplex formation between peptide nucleic acid (PNA) modified fibrils with a bridging oligonucleotide and protein-ligand recognition between mannose modified fibrils with concanavalin A. These methods to modulate hydrogel elasticity should be broadly adaptable in the context of these materials to a wide variety of molecular recognition partners.

Antibacterial Peptide-Based Gel for Prevention of Medical Implanted-Device Infection.

Implanted medical devices are prone to infection. Designing new strategies to reduce infection and implant rejection are an important challenge for modern medicine. To this end, in the last few years many hydrogels have been designed as matrices for antimicrobial molecules destined to fight frequent infection found in moist environments like the oral cavity. In this study, two types of original hydrogels containing the antimicrobial peptide Cateslytin have been designed. The first hydrogel is based on alginate modified with catechol moieties (AC gel). The choice of these catechol functional groups which derive from mussel’s catechol originates from their strong adhesion properties on various surfaces. The second type of gel we tested is a mixture of alginate catechol and thiol-terminated Pluronic (AC/PlubisSH), a polymer derived from Pluronic, a well-known biocompatible polymer. This PlubisSH polymer has been chosen for its capacity to enhance the cohesion of the composition. These two gels offer new clinical uses, as they can be injected and jellify in a few minutes. Moreover, we show these gels strongly adhere to implant surfaces and gingiva. Once gelled, they demonstrate a high level of rheological properties and stability. In particular, the dissipative energy of the (AC/PlubisSH) gel detachment reaches a high value on gingiva (10 J.m-2) and on titanium alloys (4 J.m-2), conferring a strong mechanical barrier. Moreover, the Cateslytin peptide in hydrogels exhibited potent antimicrobial activities against P. gingivalis, where a strong inhibition of bacterial metabolic activity and viability was observed, indicating reduced virulence. Gel biocompatibility tests indicate no signs of toxicity. In conclusion, these new hydrogels could be ideal candidates in the prevention and/or management of periimplant diseases.

High-Throughput Contact Flow Lithography.

High-throughput fabrication of graphically encoded hydrogel microparticles is achieved by combining flow contact lithography in a multichannel microfluidic device and a high capacity 25 mm LED UV source. Production rates of chemically homogeneous particles are improved by two orders of magnitude. Additionally, the custom-built contact lithography instrument provides an affordable solution for patterning complex microstructures on surfaces.

Nanoscale dynamics and aging of fibrous peptide-based gels.

Solutions of the aromatic dipeptide derivative molecule fluorenylmethoxycarbonyl-diphenylalanine (Fmoc-FF) in dimethyl sulfoxide produce fibrous gels when mixed with water. We study the evolution of density fluctuations of this three-component system using X-ray photon correlation spectroscopy (XPCS) and compare these results to the macroscopic rheology of the gels and optical observations of the microstructure evolution. At the investigated scattering angles, the intensity autocorrelation functions do not follow behavior expected for simple diffusion of individual Fmoc-FF molecules localized within cages of nearest neighbors. Instead, the dynamics are associated with density fluctuations on length scales of ~10-100 nm arising from disaggregation and reformation of fibers, leading to an increasingly uniform network. This process is correlated with the growth of the elastic modulus, which saturates at long times. Autocorrelation functions and relaxation times acquired from XPCS measurements are consistent with relaxation rates of structures at dynamic equilibrium. This study provides further support to the concept of exploring peptide-based gelators as valence-limited patchy particles capable of forming equilibrium gels.

De Novo Design of a Shear-Thin Recoverable Peptide-Based Hydrogel Capable of Intrafibrillar Photopolymerization

A de novo designed peptide-based gel has been prepared whose mechanical rigidity can be modulated after shear-thin recovery. The photopolymerizable β-hairpin peptide named MLD undergoes temperature-induced folding and self-assembly to afford a network of β-sheet-rich fibrils that constitutes a moderately rigid hydrogel (G′ = 220 ± 50 Pa, 1 wt %). The MLD hydrogel can be shear-thinned into a low-viscosity gel upon application of shear stress and immediately recovers its mechanical rigidity upon termination of stress. MLD peptides contain non-natural sorbamide derivatives of lysine that allow the mechanical rigidity of its hydrogels to be enhanced through polymerization of dienes displayed along the surface of the fibrils constituting the gel. Irradiation of the gel network increases its mechanical rigidity ∼2.5-fold. Circular dichroism (CD) spectroscopy shows that MLD folds and self-assembles into β-sheet-rich fibrils and that photo-cross-linking does not influence the secondary structure contained within the assembly. The MLD hydrogel shows potential as an injectable material whose mechanical properties can be modulated after delivery.