Efficient protein incorporation and release by a jigsaw-shaped self-assembling peptide hydrogel for injured brain regeneration.
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PROVIDER: S-EPMC8604910 | BioStudies |
REPOSITORIES: biostudies
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Project description:Self-assembling peptide hydrogels can be modified regarding their biodegradability, their chemical and mechanical properties and their nanofibrillar structure. Thus, self-assembling peptide hydrogels might be suitable scaffolds for regenerative therapies and tissue engineering. Owing to the use of various peptide concentrations and buffer compositions, the self-assembling peptide hydrogels might be influenced regarding their mechanical characteristics. Therefore, the mechanical properties and stability of a set of self-assembling peptide hydrogels, consisting of 11 amino acids, made from four beta sheet self-assembling peptides in various peptide concentrations and buffer compositions were studied. The formed self-assembling peptide hydrogels exhibited stiffnesses ranging from 0.6 to 205?kPa. The hydrogel stiffness was mostly affected by peptide sequence followed by peptide concentration and buffer composition. All self-assembling peptide hydrogels examined provided a nanofibrillar network formation. A maximum self-assembling peptide hydrogel dissolution of 20% was observed for different buffer solutions after 7 days. The stability regarding enzymatic and bacterial digestion showed less degradation in comparison to the self-assembling peptide hydrogel dissolution rate in buffer. The tested set of self-assembling peptide hydrogels were able to form stable scaffolds and provided a broad spectrum of tissue-specific stiffnesses that are suitable for a regenerative therapy.
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Project description:Supramolecular nanofiber peptide assemblies had been used to construct functional hydrogel biomaterials and achieved great progress. Here, a new class of biphenyl-tripeptides with different C-terminal amino acids sequences transposition were developed, which could self-assemble to form robust supramolecular nanofiber hydrogels from 0.7 to 13.8 kPa at ultra-low weight percent (about 0.27 wt%). Using molecular dynamics simulations to interrogate the physicochemical properties of designed biphenyl-tripeptide sequences in atomic detail, reasonable hydrogen bond interactions and "FF" brick (phenylalanine-phenylalanine) promoted the formation of supramolecular fibrous hydrogels. The biomechanical properties and intermolecular interactions were also analyzed by rheology and spectroscopy analysis to optimize amino acid sequence. Enhanced L929 cells adhesion and proliferation demonstrated good biocompatibility of the hydrogels. The storage modulus of BPAA-AFF with 10 nm nanofibers self-assembling was around 13.8 kPa, and the morphology was similar to natural extracellular matrix. These supramolecular nanofiber hydrogels could effectively support chondrocytes spreading and proliferation, and specifically enhance chondrogenic related genes expression and chondrogenic matrix secretion. Such biomimetic supramolecular short peptide biomaterials hold great potential in regenerative medicine as promising innovative matrices because of their simple and regular molecular structure and excellent biological performance.
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Project description:Biocompatible peptide-based supramolecular hydrogel has recently emerged as a new and promising system for biomedical applications. In this work, Rhodamine B is employed as a new capping group of self-assembling peptide, which not only provides the driving force for supramolecular nanofibrous hydrogel formation, but also endows the hydrogel with intrinsic fluroescence signal, allowing for various bioimaging applications. The fluorescent peptide nanofibrous hydrogel can be formed via disulfide bond reduction. After dilution of the hydrogel with aqueous solution, the fluorescent nanofiber suspension can be obtained. The resultant nanofibers are able to be internalized by the cancer cells and effectively track the HeLa cells for as long as 7 passages. Using a tumor-bearing mouse model, it is also demonstrated that the fluorescent supramolecular nanofibers can serve as an efficient probe for tumor imaging in a high-contrast manner.
2015-01-01 | S-EPMC4647837 | BioStudies
Project description:Traumatic brain injury (TBI) impacts over 3.17 million Americans. Management of hemorrhage and coagulation caused by vascular disruption after TBI is critical for the recovery of patients. Cerebrovascular pathologies play an important role in the underlying mechanisms of TBI. The objective of this study is to evaluate a novel regenerative medicine for the injured tissue after brain injury. We utilized a recently described synthetic growth factor with angiogenic potential to facilitate vascular growth in situ at the injury site. Previous work has shown how this injectable self-assembling peptide-based hydrogel (SAPH) creates a regenerative microenvironment for neovascularization at the injury site. Supramolecular assembly allows for thixotropy; the injectable drug delivery system provides sustained in vivo efficacy. In this study, a moderate blunt injury model was used to cause physical vascular damage and hemorrhage. The angiogenic SAPH was then applied directly on the injured rat brain. At day 7 post-TBI, significantly more blood vessels were observed than the sham and injury control group, as well as activation of VEGF-receptor 2, demonstrating the robust angiogenic response elicited by the angiogenic SAPH. Vascular markers von-Willebrand factor (vWF) and ?-smooth muscle actin (?-SMA) showed a concomitant increase with blood vessel density in response to the angiogenic SAPH. Moreover, blood brain barrier integrity and blood coagulation were also examined as the parameters to indicate wound recovery post TBI. Neuronal rescue examination by NeuN and myelin basic protein staining showed that the angiogenic SAPH may provide and neuroprotective benefit in the long-term recovery.
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Project description:Self-assembling peptides are attracting wide interest as biodegradable building blocks to achieve functional nanomaterials that do not persist in the environment. Amongst the many applications, biocatalysis is gaining momentum, although a clear structure-to-activity relationship is still lacking. This work applied emerging design rules to the heterochiral octapeptide sequence His-Leu-DLeu-Ile-His-Leu-DLeu-Ile for self-assembly into nanofibrils that, at higher concentration, give rise to a supramolecular hydrogel for the mimicry of esterase-like activity. The peptide was synthesized by solid-phase and purified by HPLC, while its identity was confirmed by 1H-NMR and electrospray ionization (ESI)-MS. The hydrogel formed by this peptide was studied with oscillatory rheometry, and the supramolecular behavior of the peptide was investigated with transmission electron microscopy (TEM) analysis, circular dichroism (CD) spectroscopy, thioflavin T amyloid fluorescence assay, and attenuated total reflectance (ATR) Fourier-transform infrared (FT-IR) spectroscopy. The biocatalytic activity was studied by monitoring the hydrolysis of p-nitrophenyl acetate (pNPA) at neutral pH, and the reaction kinetics followed an apparent Michaelis-Menten model, for which a Lineweaver-Burk plot was produced to determine its enzymatic parameters for a comparison with the literature. Finally, LC-MS analysis was conducted on a series of experiments to evaluate the extent of, if any, undesired peptide acetylation at the N-terminus. In conclusion, we provide new insights that allow gaining a clearer picture of self-assembling peptide design rules for biocatalysis.
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Project description:How do you design a peptide building block to make 2-dimentional nanowebs and 3-dimensional fibrous mats? This question has not been addressed with peptide self-assembling nanomaterials. This article describes a designed 9-residue peptide, N-Pro-Ser-Phe-Cys-Phe-Lys-Phe-Glu-Pro-C, which creates a strong fishnet-like nanostructure depending on the peptide concentrations and mechanical disruptions. This peptide is intramolecularly amphiphilic because of a single pair of ionic residues, Lys and Glu, at one end and nonionic residues, Phe, Cys, and Phe, at the other end. Circular dichroism and Fourier transform infrared spectroscopy analysis demonstrated that this peptide adopts stable beta-turn and beta-sheet structures and self-assembles into hierarchically arranged supramolecular aggregates in a concentration-dependent fashion, demonstrated by atomic force microscopy and electron microscopy. At high concentrations, the peptide dominantly self-assembled into globular aggregates that were extensively connected with each other to form "beads-on-a-thread" type nanofibers. These long nanofibers were extensively branched and overlapped to form a self-healing peptide hydrogel consisting of >99% water. This peptide can encapsulate the hydrophobic model drug pyrene and slowly release pyrene from coated microcrystals to liposomes. It can effectively stop animal bleeding within 30 s. We proposed a plausible model to interpret the intramolecular amphiphilic self-assembly process and suggest its importance for the future development of new biomaterials for drug delivery and regenerative medicine.
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Project description:Direct visualization of pathways followed by single molecules while they spontaneously self-assemble into supramolecular biological machines may provide fundamental knowledge to guide molecular therapeutics and the bottom-up design of nanomaterials and nanodevices. Here, high-speed atomic force microscopy is used to visualize self-assembly of the bidimensional lattice of protein molecules that constitutes the framework of the mature human immunodeficiency virus capsid. By real-time imaging of the assembly reaction, individual transient intermediates and reaction pathways followed by single molecules could be revealed. As when assembling a jigsaw puzzle, the capsid protein lattice is randomly built. Lattice patches grow independently from separate nucleation events whereby individual molecules follow different paths. Protein subunits can be added individually, while others form oligomers before joining a lattice or are occasionally removed from the latter. Direct real-time imaging of supramolecular self-assembly has revealed a complex, chaotic process involving multiple routes followed by individual molecules that are inaccessible to bulk (averaging) techniques.
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Project description:Self-assembly of peptides is a powerful method of preparing nanostructured materials. These peptides frequently utilize charged groups as a convenient switch for controlling self-assembly in which pH or ionic strength determines the assembly state. Multidomain peptides have been previously designed with charged domains of amino acids, which create molecular frustration between electrostatic repulsion and a combination of supramolecular forces including hydrogen bonding and hydrophobic packing. This frustration is eliminated by the addition of multivalent ions or pH adjustment, resulting in a self-assembled hydrogel. However, these charged functionalities can have profound, unintended effects on the properties of the resulting material. Access to neutral self-assembled nanostructured hydrogels may allow for distinct biological properties that are not available to highly charged analogues. Here, we designed a series of peptides to determine if self-assembly could be mediated by the steric interactions created by neutral hydroxyproline (O) domains, eliminating the need for charged residues and creating a neutral peptide hydrogel. The series of peptides, O n (SL)6O n , was studied to determine the effect of oligo-hydroxyproline on peptide self-assembly and nanostructure. We show that peptide solubility and nanofiber length increase with a higher number of hydroxyproline residues. Within this series, O5(SL)6O5 displayed the optimal properties for self-assembly and hydrogelation. In vitro, this hydrogel supports cell viability of fibroblasts, while in vivo it is infiltrated with cells and easily degraded over time without promoting a strong inflammatory response. This neutral self-assembling peptide hydrogel shows promising properties for biomedical, cell preservation, and tissue regeneration applications.
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Project description:Neurocognitive disorders are an important societal challenge and the need for early prevention is increasingly recognized. Meta-analyses show beneficial effects of cognitive activities on cognition. However, high financial costs, low intrinsic motivation, logistic challenges of group-based activities, or the need to operate digital devices prevent their widespread application in clinical practice. Solving jigsaw puzzles is a cognitive activity without these hindering characteristics, but cognitive effects have not been investigated yet. With this study, we aim to evaluate the effect of solving jigsaw puzzles on visuospatial cognition, daily functioning, and psychological outcomes.The pre-posttest, assessor-blinded study will include 100 cognitively healthy adults 50 years of age or older, who will be randomly assigned to a jigsaw puzzle group or a cognitive health counseling group. Within the 5-week intervention period, participants in the jigsaw puzzle group will engage in 30 days of solving jigsaw puzzles for at least 1 h per day and additionally receive cognitive health counseling. The cognitive health counseling group will receive the same counseling intervention but no jigsaw puzzles. The primary outcome, global visuospatial cognition, will depict the average of the z-standardized performance scores in visuospatial tests of perception, constructional praxis, mental rotation, processing speed, flexibility, working memory, reasoning, and episodic memory. As secondary outcomes, we will assess the eight cognitive abilities, objective and subjective visuospatial daily functioning, psychological well-being, general self-efficacy, and perceived stress. The primary data analysis will be based on mixed-effects models in an intention-to-treat approach.Solving jigsaw puzzles is a low-cost, intrinsically motivating, cognitive leisure activity, which can be executed alone or with others and without the need to operate a digital device. In the case of positive results, these characteristics allow an easy implementation of solving jigsaw puzzles in clinical practice as a way to improve visuospatial functioning. Whether cognitive impairment and loss of independence in everyday functioning might be prevented or delayed in the long run has to be examined in future studies.ClinicalTrials.gov, NCT02667314 . Registered on 27 January 2016.
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Project description:Progress in self-assembly and supramolecular chemistry has been directed toward obtaining macromolecular assemblies with higher degrees of complexity, simulating the highly structured environment in natural systems. One approach to this type of complexity are multistep, multicomponent, self-assembling systems that allow approaches comparable to traditional multistep synthetic organic chemistry; however, only a few examples of this approach have appeared in the literature. Our previous work demonstrated nanofibrous mimics of the extracellular matrix. Here we demonstrate the ability to create a unique hydrogel, developed by stepwise self-assembly of multidomain peptide fibers and liposomes. The two-component system allows for controlled release of bioactive factors at multiple time points. The individual components of the self-assembled gel and the composite hydrogel were characterized by TEM, SEM, and rheometry, demonstrating that peptide nanofibers and lipid vesicles both retain their structural integrity in the composite gel. The rheological robustness of the hydrogel is shown to be largely unaffected by the presence of liposomes. Release studies from the composite gels loaded with different growth factors EGF, MCP-1, and PlGF-1 showed delay and prolongation of release by liposomes entrapped in the hydrogel compared to more rapid release from the hydrogel alone. This bimodal release system may have utility in systems where timed cascades of biological signals may be valuable, such as in tissue regeneration.
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