Tuning viscoelastic properties of supramolecular peptide gels via dynamic covalent crosslinking

A dynamic covalent crosslinking approach is used to crosslink supramolecular peptide gels. This novel approach facilitates tuning viscoelastic properties of the gel and enhances mechanical stability (storage modulus exceeding 105 Pa) of the peptide gels. This journal is © The Royal Society of Chemistry 2015

Supramolecular chirality in self-assembled peptide amphiphile nanostructures

Induced supramolecular chirality was investigated in the self-assembled peptide amphiphile (PA) nanosystems. Having shown that peptide chirality can be transferred to the covalently-attached achiral pyrene moiety upon PA self-assembly, the chiral information is transferred to molecular pyrene via weak noncovalent interactions. In the first design of a supramolecular chiral system, the chromophore was covalently attached to a peptide sequence (VVAGH) via an ε-aminohexanoic acid spacer. Covalent attachment yielded a PA molecule self-assembling into nanofibers. In the second design, the chromophore was encapsulated within the hydrophobic core of self-assembled nanofibers of another PA consisting of the same peptide sequence attached to lauric acid. We observed that supramolecular chirality was induced in the chromophore by PA assembly into chiral nanostructures, whether it was covalently attached, or noncovalently bound. © The Royal Society of Chemistry 2015

Heparin mimetic peptide nanofiber gel promotes regeneration of full thickness burn injury

Burn injuries are one of the most common types of trauma worldwide, and their unique physiology requires the development of specialized therapeutic materials for their treatment. Here, we report the use of synthetic, functional and biodegradable peptide nanofiber gels for the improved healing of burn wounds to alleviate the progressive loss of tissue function at the post-burn wound site. These bioactive nanofiber gels form scaffolds that recapitulate the structure and function of the native extracellular matrix through signaling peptide epitopes, which can trigger angiogenesis through their affinity to basic growth factors. In this study, the angiogenesis-promoting properties of the bioactive scaffolds were utilized for the treatment of a thermal burn model. Following the excision of necrotic tissue, bioactive gels and control solutions were applied topically onto the wound area. The wound healing process was evaluated at 7, 14 and 21 days following injury through histological observations, immunostaining and marker RNA/protein analysis. Bioactive peptide nanofiber-treated burn wounds formed well-organized and collagen-rich granulation tissue layers, produced a greater density of newly formed blood vessels, and exhibited increased re-epithelialization and skin appendage development with minimal crust formation, while non-bioactive peptide nanofibers and the commercial wound dressing 3M™ Tegaderm™ did not exhibit significant efficiency over sucrose controls. Overall, the heparin-mimetic peptide nanofiber gels increased the rate of repair of burn injuries and can be used as an effective means of facilitating wound healing. © 2017 Elsevier Lt

Self-assembled template-directed synthesis of one-dimensional silica and titania nanostructures

Mineralized biological materials such as shells, skeleton, and teeth experience biomineralization. Biomimetic materials exploit the biomineralization process to form functional organic-inorganic hybrid nanostructures. In this work, we mimicked the biomineralization process by the de novo design of an amyloid-like peptide that self-assembles into nanofibers. Chemically active groups enhancing the affinity for metal ions were used to accumulate silicon and titanium precursors on the organic template. The self-assembly process and template effect were characterized by CD, FT-IR, UV-vis, fluorescence, rheology, TGA, SEM, and TEM. The self-assembled organic nanostructures were exploited as a template to form high-aspect-ratio 1-D silica and titania nanostructures by the addition of appropriate precursors. Herein, a new bottom-up approach was demonstrated to form silica and titania nanostructures that can yield wide opportunities to produce high-aspect-ratio inorganic nanostructures with high surface areas. The materials developed in this work have vast potential in the fields of catalysis and electronic materials. © 2011 American Chemical Society

Selective adhesion and growth of vascular endothelial cells on bioactive peptide nanofiber functionalized stainless steel surface

Metal-based scaffolds such as stents are the most preferred treatment methods for coronary artery disease. However, impaired endothelialization on the luminal surface of the stents is a major limitation occasionally leading to catastrophic consequences in the long term. Coating the stent surface with relevant bioactive molecules is considered to aid in recovery of endothelium around the wound site. However, this strategy remains challenging due to restrictions in availability of proper bioactive signals that will selectively promote growth of endothelium and the lack of convenience for immobilization of such signaling molecules on the metal surface. In this study, we developed self-assembled peptide nanofibers that mimic the native endothelium extracellular matrix and that are securely immobilized on stainless steel surface through mussel-inspired adhesion mechanism. We synthesized Dopa-conjugated peptide amphiphile and REDV-conjugated peptide amphiphile that are self-assembled at physiological pH. We report that Dopa conjugation enabled nanofiber coating on stainless steel surface, which is the most widely used backbone of the current stents. REDV functionalization provided selective growth of endothelial cells on the stainless steel surface. Our results revealed that adhesion, spreading, viability and proliferation rate of vascular endothelial cells are remarkably enhanced on peptide nanofiber coated stainless steel surface compared to uncoated surface. On the other hand, although vascular smooth muscle cells exhibited comparable adhesion and spreading profile on peptide nanofibers, their viability and proliferation significantly decreased. Our design strategy for surface bio-functionalization created a favorable microenvironment to promote endothelial cell growth on stainless steel surface, thereby providing an efficient platform for bioactive stent development for long term treatment of cardiovascular diseases. © 2011 Elsevier Ltd

Self-assembled one-dimensional soft nanostructures

The self-assembly process is a bottom-up approach and is the spontaneous aggregation of many different subunits into well-defined functional structures with varying properties. Self-assembly is an attractive method to develop one-dimensional nanostructures and is controlled by many factors including temperature, pH and electrolyte addition. Novel self-assembled one-dimensional nanostructures are finding applications in regenerative medicine and electronics as well as in fabrication of nanoscale electronic, mechanic, magnetic, optical, and combinatorial devices. Their utility comes from their high ratio of surface area to volume, and their quantum-confinement effects. This paper reviews one-dimensional self-assembled organic nanostructures classified according to the non-covalent forces acting on their formation. © 2010 The Royal Society of Chemistry

Glycosaminoglycan-Mimetic Signals Direct the Osteo/Chondrogenic Differentiation of Mesenchymal Stem Cells in a Three-Dimensional Peptide Nanofiber Extracellular Matrix Mimetic Environment

Recent efforts in bioactive scaffold development focus strongly on the elucidation of complex cellular responses through the use of synthetic systems. Designing synthetic extracellular matrix (ECM) materials must be based on understanding of cellular behaviors upon interaction with natural and artificial scaffolds. Hence, due to their ability to mimic both the biochemical and mechanical properties of the native tissue environment, supramolecular assemblies of bioactive peptide nanostructures are especially promising for development of bioactive ECM-mimetic scaffolds. In this study, we used glycosaminoglycan (GAG) mimetic peptide nanofiber gel as a three-dimensional (3D) platform to investigate how cell lineage commitment is altered by external factors. We observed that amount of fetal bovine serum (FBS) presented in the cell media had synergistic effects on the ability of GAG-mimetic nanofiber gel to mediate the differentiation of mesenchymal stem cells into osteogenic and chondrogenic lineages. In particular, lower FBS concentration in the culture medium was observed to enhance osteogenic differentiation while higher amount FBS promotes chondrogenic differentiation in tandem with the effects of the GAG-mimetic 3D peptide nanofiber network, even in the absence of externally administered growth factors. We therefore demonstrate that mesenchymal stem cell differentiation can be specifically controlled by the combined influence of growth medium components and a 3D peptide nanofiber environment. © 2016 American Chemical Society

Controlled enzymatic stability and release characteristics of supramolecular chiral peptide amphiphile nanofiber gels

Supramolecular bioarchitectures formed by assembly of achiral or chiral building blocks play important roles in various biochemical processes. Stereochemistry of amino acids is important for structural organization of peptide and protein assemblies and structure-microenvironment interactions. In this study, oppositely charged peptide amphiphile (PA) molecules with L-, D- and mixture of L- and D-amino acid conformations are coassembled into supramolecular nanofibers and formed self-supporting gels at pH 7.4 in water. The enzymatic stability of the PA nanofiber gels was studied in the presence of proteinase K enzyme, which digest a broad spectrum of proteins and peptides. The structural changes on the chiral PA nanofibers were also analyzed at different time periods in the presence of enzymatic activity. Controlled release of a model cargo molecule through the chiral PA nanofiber gels was monitored. The diffusivity parameters were measured for all gel systems. Release characteristics and the enzymatic stability of the peptide nanofiber gels were modulated depending on organization of the chiral PA molecules within the supramolecular assemblies. © 2017 Elsevier B.V

Inhibition of VEGF mediated corneal neovascularization by anti-angiogenic peptide nanofibers

Atypical angiogenesis is one of the major symptoms of severe eye diseases, including corneal neovascularization, and the complex nature of abnormal vascularization requires targeted methods with high biocompatibility. The targeting of VEGF is the most common approach for preventing angiogenesis, and the LPPR peptide sequence is known to strongly inhibit VEGF activity by binding to the VEGF receptor neuropilin-1. Here, the LPPR epitope is presented on a peptide amphiphile nanofiber system to benefit from multivalency and increase the anti-angiogenic function of the epitope. Peptide amphiphile nanofibers are especially useful for ocular delivery applications due to their ability to remain on the site of interest for extended periods of time, facilitating the long-term presentation of bioactive sequences. Consequently, the LPPR sequence was integrated into a self-assembled peptide amphiphile network to increase its efficiency in the prevention of neovascularization. Anti-angiogenic effects of the peptide nanofibers were investigated by using both in vitro and in vivo models. LPPR-PA nanofibers inhibited endothelial cell proliferation, tube formation, and migration to a greater extent than the soluble LPPR peptide in vitro. In addition, the LPPR-PA nanofiber system led to the prevention of vascular maturation and the regression of angiogenesis in a suture-induced corneal angiogenesis model. These results show that the anti-angiogenic activity exhibited by LPPR peptide nanofibers may be utilized as a promising approach for the treatment of corneal angiogenesis. © 2016 Elsevier Lt

Catalytic supramolecular self-assembled peptide nanostructures for ester hydrolysis

Essential amino acids in catalytic sites of native enzymes are important in nature inspired catalyst designs. Active sites of enzymes contain the coordinated assembly of multiple amino acids, and catalytic action is generated by the dynamic interactions among multiple residues. However, catalysis studies are limited by the complex and dynamic structure of the enzyme; and it is difficult to exclusively attribute a given function to a specific residue. Minimalistic approaches involving artificial catalytic sites are promising for the investigation of the enzyme function in the absence of non-essential protein components, and self-assembling peptide nanostructures are especially advantageous in this context. Here we demonstrate the design and characterization of an enzyme-mimetic catalytic nanosystem presenting essential residues (Ser, His, Asp). The function of each residue and its combinations on the nanostructures in hydrolysis reaction was studied. The catalytic self-assembled nanostructures were used for efficient ester hydrolysis such as a model substrate (pNPA) and a natural substrate (acetylcholine) highlighting the key role of self-assembly in catalytic domain formation to test the efficiency of the de novo designed catalyst as a catalytic triad model. © The Royal Society of Chemistry 2016