Enhancing the Biological Functionality of Hydrogels Using Self-Assembling Peptides.

The self-assembly of peptides and proteins into amyloid fibrils of nanometric thickness and up to several micrometres in length, a phenomenon widely observed in biological systems, has recently aroused a growing interest in nanotechnology and nanomedicine. Here we have applied atomic force microscopy and single molecule force spectroscopy to study the amyloidogenesis of a peptide derived from human amylin and of its reverse sequence. The spontaneous formation of protofibrils and their orientation along well-defined directions on graphite and DMSO-coated graphite substrates make the studied peptides interesting candidates for nanotechnological applications. The measured binding forces between peptides correlate with the number of hydrogen bonds between individual peptides inside the fibril structure according to molecular dynamics simulations.

Self-assembling peptides (SAPs) have enormous potential in medical and biological applications, particularly noninvasive tumor therapy. SAPs self-assembly is governed by multiple non-covalent interactions and results in the formation of a variety of morphological features. SAPs can be assembled in a variety of ways, including chemical conjugation and physical encapsulation, to incorporate multiple bioactive motifs. Peptide-based nanomaterials are used for chemotherapy, delivery vehicles, immunotherapy, and noninvasive tumor therapies (e.g. photodynamic therapy) by employing the self-assembling properties of peptides. The recent increase of SAPs is almost entirely due to their excellent biocompatibility, responsiveness toward tumor microenvironment, multivalency, and structural versatility. Synergistic therapy is a more effective and powerful approach to treat the tumor. Notably, SAPs can be used to subtly combine various treatments. Importantly, SAPs are capable of subtly making the combination of various treatments. This review describes mechanisms of peptides self-assemble into various structures and their biomedical applications with a focus on possible treatments.

Intervention of biophysical effects generated by self-assembly peptides in tumor progression.

This review focuses on the application of two classes of peptides, i.e., self-assembling peptides (SAPs) and cell-targeting peptides (CTPs), in the development of nanocarrier delivery systems. Self-assembling peptides are emerging in a wide range of biomedical and bioengineering applications and fall into several classes, including peptide amphiphilies, bolaamphiphile peptides, cyclic peptides, and ionic complementary peptides, which can be found naturally or synthesized. The advantage of synthesizing peptides is that their self-assembling properties can be exploited to form desirable structures for various applications. Another, unique property of self-assembling peptides, is stimuli-responsibility in different environments including various pHs, temperatures, ionic strengths, etc. These characteristics make peptides applicable in a wide range of biomaterials in drug discovery. This study reviews the design principles of well-known self-assembling peptides, as well as their physical/chemical properties. In addition, it discusses the therapeutic cancer-targeting peptides and current combinatorial peptide library methods used to identify targeting peptides. Cancer-targeting peptides can target either tumor cell surfaces or tumor vasculature. The RGD peptide is one of the first tumor-targeting peptides that can bind to self-assembling peptides or any other nanocarrier to improve the therapeutic efficiency of targeting drug delivery systems.

Self-assembling peptides are rapidly gaining attention as novel biomaterials for food and biomedical applications. Peptides self-assemble when triggered by physical or chemical factors due to their versatile physicochemical characteristics. Peptide self-assembly, when combined with the health-promoting bioactivity of peptides, can also result in a plethora of biofunctionalities of the biomaterials. This perspective highlights current developments in the use of food-derived self-assembling peptides as biomaterials, bioactive nutraceuticals, and potential dual functioning bioactive biomaterials. Also discussed are the challenges and opportunities in the use of self-assembling bioactive peptides in designing biocompatible, biostable, and bioavailable multipurpose biomaterials.

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...

Under appropriate physicochemical conditions, short peptide fragments and their synthetic mimics have been shown to form elongated cross-β nanostructures through self-assembly. The self-assembly process and the resultant peptide nanostructures are not only related to neurodegenerative diseases but also provide inspiration for the development of novel bionanomaterials. Both experimental and theoretical studies on peptide self-assembly have shown that the self-assembly process spans multiple time and length scales and is hierarchical. β-sheet self-assembly consists of three sub-processes from the microscopic to the mesoscopic level: β-sheet locking, lateral stacking, and morphological transformation. Detailed atomistic simulation studies have provided insight into the early stages of peptide nanostructure formation and the interplay between different non-covalent interactions at the microscopic level. This review gives a brief introduction of the hierarchical peptide self-assembly process and focuses on the roles of various non-covalent interactions in the sub-processes based on recent simulation, experimental, and theoretical studies.

Self-assembling peptides are promising biomaterials for spinal cord repair as they can easily be injected into the lesion site and can provide physical support to regrowing nervous tissue. However, to improve upon the design of synthetic scaffolds for spinal cord injury, characteristics of the scaffold/host relationship need to be further investigated. In the current study we aimed to evaluate both the mechanical properties and the therapeutic effect of two self-assembling peptides B24 and biotin-LDLK12 in spinal cord injury. Atomic force microscopy and rheology were used to characterise various concentrations of the two peptides in terms of the propensity to form nanostructures and the viscoelastic properties. Concurrently, these peptide solutions were injected into the contused spinal cord of rats to evaluate both diffusibility within the tissue, and scaffold formation in vivo. After selection of the best concentration for delivery in vivo, the two self-assembling peptides were tested in the contused spinal cord of rats for their influence on hematoma and cyst formation, biocompatibility and permissiveness for axonal growth. The results suggest that rheology can provide a useful indication to predict the hydrogel formation and diffusibility of the self-assembling peptides in vivo. Moreover at three days post-injury both self-assembling peptides had a good hemostatic effect and at 28 days they improved axon regrowth. In summary, the injectable self-assembling hydrogels could attenuate hematoma and provide a therapeutic effect in a spinal cord injury model.

Self-assembling into aggregates with defined structures is a common phenomenon for many peptides at high concentrations. In this study, we found that when PTP-7b (FLGALFKALSHLL), a concentration-dependent self-assembling peptide, bound to tissue cells and accumulated on cell surfaces, it migrated and self-assembled into exosome-like aggregates at certain locations on the cell membranes. Studies using confocal microscopy and scanning electron microscopy revealed that peptide PTP-7b induced cell tissue damage through a new cell lysis mechanism that involved peptide self-assembly on cell surfaces, extracting lipids from cell membranes, and transporting peptides into the cytoplasm. Peptide self-assembly attributed greatly to peptide-cell interactions and thus the biological activity of a peptide. Because peptide self-assembly was a slow process, PTP-7b-induced cell lysis showed a biphasic behavior: a gradual viability decrease was followed by a rapid decline. These results suggest that peptide self-assembly could be equally as important as charge and secondary structure of a peptide in determining the anticancer and antibacterial activities of therapeutic peptides.

Self-assembled peptide and protein nanostructures for anti-cancer therapy: Targeted delivery, stimuli-responsive devices and immunotherapy.

Design Principles of Self-assembling Peptides and Their Potential Applications

A comprehensive review on peptide-bearing biomaterials: From ex situ to in situ self-assembly

Peptide-based hydrogels are of interest for their potential use in regenerative medicine. Combining these hydrogels with materials that may enhance their physical and biological properties, such as glycosaminoglycans, has the potential to extend their range of biomedical applications, for example in the repair of early cartilage degeneration. The aim of this study was to combine three self-assembling peptides (P11 -4, P11 -8, and P11 -12) with chondroitin sulphate at two molar ratios of 1:16 and 1:64 in 130 and 230mM Na+ salt concentrations. The study investigates the effects of mixing self-assembling peptide and glycosaminoglycan on the physical and mechanical properties at 37°C. Peptide alone, chondroitin sulphate alone, and peptide in combination with chondroitin sulphate were analysed using Fourier transform infrared spectroscopy to determine the β-sheet percentage, transmission electron microscopy to determine the fibril morphology, and rheology to determine the elastic and viscous modulus of the materials. All of the variables (peptide, salt concentration, and chondroitin sulphate molar ratio) had an effect on the mechanical properties, β-sheet formation, and fibril morphology of the hydrogels. P11 -4 and P11 -8-chondroitin sulphate mixtures, at both molar ratios, were shown to have a high β-sheet percentage, dense entangled fibrillar networks, as well as high mechanical stiffness in both (130 and 230mM) Na+ salt solutions when compared with the P11 -12/chondroitin sulphate mixtures. These peptide/chondroitin sulphate hydrogels show promise for biomedical applications in glycosaminoglycan depleted tissues.

Matrix metalloproteinases (MMPs) play critical roles in numerous physiological processes and are essential for various fundamental biological activities. Alterations in their expression levels have been associated with multiple diseases and pathological conditions. The self-assembly of small-molecule peptides into hydrogels and nanomaterials has been widely investigated for its various biomedical applications. MMPs can trigger enzyme-instructed assemblies of peptides with specific sequences to form various hydrogels for potential applications in treating several diseases, including cancer, inflammation, wound healing, myocardial infarction, and central nervous system disease, and in tissue engineering. In addition, MMPs can also trigger the self-assembly of peptides into a variety of nanostructures tailored on demand, especially serving as indicators and activators to increase their functionality in sensing applications and controlled substance release, acting as primitive biological triggers, modulating biological responses, ensuring the targeted delivery of biomolecules to specific locations, and inducing changes in the self-assembled peptide nanostructures by introducing enzyme cleavage site recognition sequences to release loaded drugs, which is crucial for applications in hydrogels and nanomaterials. This review summarizes and highlights the successful applications of various MMP-triggered self-assembled peptide hydrogels and nanostructures over the past decade and emphasizes their potential for controlled drug delivery, targeted therapy, and intelligent biomaterial-assisted wound regeneration and healing. Furthermore, future opportunities and challenges in this field are reviewed.

The natural biomolecules of peptides and proteins are able to form elegant metal incorporating supramolecular nanomaterials through multiple weak non-covalent interactions. The use of toxic chemical reagents to fabricate silver nanoparticles poses a danger to apply them in various biomedical applications. Peptide and protein biomolecules have the potential to overcome this barrier by the supramolecular chemistry approach. In this review, we focus on the self-assembly of peptides and proteins to synthesize silver incorporating supramolecular nanoarchitectures, which in turn enhance the biological properties of these silver nanomaterials being used in nanomedicine. This review aims to illustrate the recent developments in amphiphilic peptides, oligopeptides, collagen, bovine serum albumin (BSA), and human serum albumin (HSA) as capping, stabilizing, and reducing agents to form silver incorporating supramolecular nanostructures. Finally, we provide some biomedical applications of silver-incorporating supramolecular nanomaterials along with future perspectives.