Self‐assembly of peptide amphiphiles: From molecules to nanostructures to biomaterials
TL;DR: The strategies for using molecular self‐assembly as a toolbox to produce peptide amphiphile nanostructures and materials are highlighted and efforts to translate this technology into applications as therapeutics are reviewed.
Abstract: Peptide amphiphiles are a class of molecules that combine the structural features of amphiphilic surfactants with the functions of bioactive peptides and are known to assemble into a variety of nanostructures. A specific type of peptide amphiphiles are known to self-assemble into one-dimensional nanostructures under physiological conditions, predominantly nanofibers with a cylindrical geometry. The resultant nanostructures could be highly bioactive and are of great interest in many biomedical applications, including tissue engineering, regenerative medicine, and drug delivery. In this context, we highlight our strategies for using molecular self-assembly as a toolbox to produce peptide amphiphile nanostructures and materials and efforts to translate this technology into applications as therapeutics. We also review our recent progress in using these materials for treating spinal cord injury, inducing angiogenesis, and for hard tissue regeneration and replacement.
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TL;DR: The ability to design COFs and to adjust their pore metrics using the principles of reticular synthesis has given rise to frameworks with ultralow densities, which has resulted in the first implementation of the concept of molecular weaving.
Abstract: Just over a century ago, Lewis published his seminal work on what became known as the covalent bond, which has since occupied a central role in the theory of making organic molecules. With the advent of covalent organic frameworks (COFs), the chemistry of the covalent bond was extended to two- and three-dimensional frameworks. Here, organic molecules are linked by covalent bonds to yield crystalline, porous COFs from light elements (boron, carbon, nitrogen, oxygen, and silicon) that are characterized by high architectural and chemical robustness. This discovery paved the way for carrying out chemistry on frameworks without losing their porosity or crystallinity, and in turn achieving designed properties in materials. The recent union of the covalent and the mechanical bond in the COF provides the opportunity for making woven structures that incorporate flexibility and dynamics into frameworks.
1,687 citations
TL;DR: The nanocomposite nature of the extracellular matrix is reviewed, the design considerations for different tissues are described, and the impact of nanostructures on the properties of scaffolds and their uses in monitoring the behaviour of engineered tissues are discussed.
Abstract: Tissue engineering aims at developing functional substitutes for damaged tissues and organs. Before transplantation, cells are generally seeded on biomaterial scaffolds that recapitulate the extracellular matrix and provide cells with information that is important for tissue development. Here we review the nanocomposite nature of the extracellular matrix, describe the design considerations for different tissues and discuss the impact of nanostructures on the properties of scaffolds and their uses in monitoring the behaviour of engineered tissues. We also examine the different nanodevices used to trigger certain processes for tissue development, and offer our view on the principal challenges and prospects of applying nanotechnology in tissue engineering.
1,272 citations
TL;DR: The different types of materials used as delivery vehicles for chemotherapeutic agents and their structural characteristics that improve the therapeutic efficacy of their drugs are discussed and recent scientific advances in the area of chemotherapy are described.
Abstract: Although conventional chemotherapy has been successful to some extent, the main drawbacks of chemotherapy are its poor bioavailability, high-dose requirements, adverse side effects, low therapeutic indices, development of multiple drug resistance, and non-specific targeting. The main aim in the development of drug delivery vehicles is to successfully address these delivery-related problems and carry drugs to the desired sites of therapeutic action while reducing adverse side effects. In this review, we will discuss the different types of materials used as delivery vehicles for chemotherapeutic agents and their structural characteristics that improve the therapeutic efficacy of their drugs and will describe recent scientific advances in the area of chemotherapy, emphasizing challenges in cancer treatments.
1,229 citations
TL;DR: Poly(dopamine) is not a covalent polymer but instead a supramolecular aggregate of monomers (consisting primarily of 5,6-dihydroxyindoline and its dione derivative) that are held together through a combination of charge transfer, π-stacking, and hydrogen bonding interactions.
Abstract: Herein we propose a new structure for poly(dopamine), a synthetic eumelanin that has found broad utility as an antifouling agent. Commercially available 3-hydroxytyramine hydrochloride (dopamine HCl) was polymerized under aerobic, aqueous conditions using tris(hydroxymethyl)aminomethane (TRIS) as a basic polymerization initiator, affording a darkly colored powder product upon isolation. The polymer was analyzed using a variety of solid state spectroscopic and crystallographic techniques. Collectively, the data showed that in contrast to previously proposed models, poly(dopamine) is not a covalent polymer but instead a supramolecular aggregate of monomers (consisting primarily of 5,6-dihydroxyindoline and its dione derivative) that are held together through a combination of charge transfer, π-stacking, and hydrogen bonding interactions.
897 citations
TL;DR: This review focuses on the influence of thermodynamic and kinetic factors on structural assembly and regulation based on different types of peptide building blocks, including aromatic dipeptides, amphiphilic peptides, polypeptide, and amyloid-relevant peptides.
Abstract: Self-assembling systems play a significant role in physiological functions and have therefore attracted tremendous attention due to their great potential for applications in energy, biomedicine and nanotechnology. Peptides, consisting of amino acids, are among the most popular building blocks and programmable molecular motifs. Nanostructures and materials assembled using peptides exhibit important potential for green-life new technology and biomedical applications mostly because of their bio-friendliness and reversibility. The formation of these ordered nanostructures pertains to the synergistic effect of various intermolecular non-covalent interactions, including hydrogen-bonding, π–π stacking, electrostatic, hydrophobic, and van der Waals interactions. Therefore, the self-assembly process is mainly driven by thermodynamics; however, kinetics is also a critical factor in structural modulation and function integration. In this review, we focus on the influence of thermodynamic and kinetic factors on structural assembly and regulation based on different types of peptide building blocks, including aromatic dipeptides, amphiphilic peptides, polypeptides, and amyloid-relevant peptides.
657 citations
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TL;DR: The ability of fibronectin to bind cells can be accounted for by the tetrapeptide L-arginyl-glycyl- L-aspartyl-L-serine, a sequence which is part of the cell attachment domain of fibronsectin and present in at least five other proteins.
Abstract: The ability of fibronectin to bind cells can be accounted for by the tetrapeptide L-arginyl-glycyl-L-aspartyl-L-serine, a sequence which is part of the cell attachment domain of fibronectin and present in at least five other proteins. This tetrapeptide may constitute a cellular recognition determinant common to several proteins.
3,574 citations
TL;DR: In this paper, pH-induced self-assembly of a peptide-amphiphile was used to make a nanostructured fibrous scaffold reminiscent of extracellular matrix.
Abstract: We have used the pH-induced self-assembly of a peptide-amphiphile to make a nanostructured fibrous scaffold reminiscent of extracellular matrix. The design of this peptide-amphiphile allows the nanofibers to be reversibly cross-linked to enhance or decrease their structural integrity. After cross-linking, the fibers are able to direct mineralization of hydroxyapatite to form a composite material in which the crystallographic c axes of hydroxyapatite are aligned with the long axes of the fibers. This alignment is the same as that observed between collagen fibrils and hydroxyapatite crystals in bone.
3,125 citations
TL;DR: Chondroitin and keratan sulphate proteoglycans are among the main inhibitory extracellular matrix molecules that are produced by reactive astrocytes in the glial scar, and they are believed to play a crucial part in regeneration failure.
Abstract: After injury to the adult central nervous system (CNS), injured axons cannot regenerate past the lesion. In this review, we present evidence that this is due to the formation of a glial scar. Chondroitin and keratan sulphate proteoglycans are among the main inhibitory extracellular matrix molecules that are produced by reactive astrocytes in the glial scar, and they are believed to play a crucial part in regeneration failure. We will focus on this role, as well as considering the behaviour of regenerating neurons in the environment of CNS injury.
2,838 citations
TL;DR: The artificial nanofiber scaffold induced very rapid differentiation of cells into neurons, while discouraging the development of astrocytes, linked to the amplification of bioactive epitope presentation to cells by the nanofibers.
Abstract: Neural progenitor cells were encapsulated in vitro within a three-dimensional network of nanofibers formed by self-assembly of peptide amphiphile molecules. The self-assembly is triggered by mixing cell suspensions in media with dilute aqueous solutions of the molecules, and cells survive the growth of the nanofibers around them. These nanofibers were designed to present to cells the neurite-promoting laminin epitope IKVAV at nearly van der Waals density. Relative to laminin or soluble peptide, the artificial nanofiber scaffold induced very rapid differentiation of cells into neurons, while discouraging the development of astrocytes. This rapid selective differentiation is linked to the amplification of bioactive epitope presentation to cells by the nanofibers.
2,081 citations
TL;DR: The scope of amino acid selection and alkyl tail modification in the peptide-amphiphile molecules are investigated, yielding nanofibers varying in morphology, surface chemistry, and potential bioactivity, demonstrating the chemically versatile nature of this supramolecular system.
Abstract: Twelve derivatives of peptide-amphiphile molecules, designed to self-assemble into nanofibers, are described. The scope of amino acid selection and alkyl tail modification in the peptide-amphiphile molecules are investigated, yielding nanofibers varying in morphology, surface chemistry, and potential bioactivity. The results demonstrate the chemically versatile nature of this supramolecular system and its high potential for manufacturing nanomaterials. In addition, three different modes of self-assembly resulting in nanofibers are described, including pH control, divalent ion induction, and concentration.
1,266 citations