Tunable Mechanical Properties of Ultrasmall Peptide Hydrogels by Crosslinking and Functionalization to Achieve the 3D Distribution of Cells

Seow, Wei Yang; Hauser, Charlotte

doi:10.1002/adhm.201200463

Cited by 37 publications

(44 citation statements)

References 33 publications

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“…The peptide solutions (20 mM, 250 µL) were pipetted into a polystyrene ring mold as described previously [104]. The solutions were allowed to gel at ambient temperature (22°C) over 24 hours before rheological measurements were carried out.…”

Section: Methodsmentioning

confidence: 99%

De Novo Design and Experimental Characterization of Ultrashort Self-Associating Peptides

Smadbeck

Chan²,

Khoury³

et al. 2014

PLoS Comput Biol

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Self-association is a common phenomenon in biology and one that can have positive and negative impacts, from the construction of the architectural cytoskeleton of cells to the formation of fibrils in amyloid diseases. Understanding the nature and mechanisms of self-association is important for modulating these systems and in creating biologically-inspired materials. Here, we present a two-stage de novo peptide design framework that can generate novel self-associating peptide systems. The first stage uses a simulated multimeric template structure as input into the optimization-based Sequence Selection to generate low potential energy sequences. The second stage is a computational validation procedure that calculates Fold Specificity and/or Approximate Association Affinity (K*association) based on metrics that we have devised for multimeric systems. This framework was applied to the design of self-associating tripeptides using the known self-associating tripeptide, Ac-IVD, as a structural template. Six computationally predicted tripeptides (Ac-LVE, Ac-YYD, Ac-LLE, Ac-YLD, Ac-MYD, Ac-VIE) were chosen for experimental validation in order to illustrate the self-association outcomes predicted by the three metrics. Self-association and electron microscopy studies revealed that Ac-LLE formed bead-like microstructures, Ac-LVE and Ac-YYD formed fibrillar aggregates, Ac-VIE and Ac-MYD formed hydrogels, and Ac-YLD crystallized under ambient conditions. An X-ray crystallographic study was carried out on a single crystal of Ac-YLD, which revealed that each molecule adopts a β-strand conformation that stack together to form parallel β-sheets. As an additional validation of the approach, the hydrogel-forming sequences of Ac-MYD and Ac-VIE were shuffled. The shuffled sequences were computationally predicted to have lower K*association values and were experimentally verified to not form hydrogels. This illustrates the robustness of the framework in predicting self-associating tripeptides. We expect that this enhanced multimeric de novo peptide design framework will find future application in creating novel self-associating peptides based on unnatural amino acids, and inhibitor peptides of detrimental self-aggregating biological proteins.

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Section: Methodsmentioning

confidence: 99%

De Novo Design and Experimental Characterization of Ultrashort Self-Associating Peptides

Smadbeck

Chan²,

Khoury³

et al. 2014

PLoS Comput Biol

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“…Due to their small size these peptides are attractive, since they offer a cheap production alternative to other protein or peptide-based structures with longer sequences. 106,164 In a recent study, 165 the integrin-recognition motif RGD was conjugated to the hexamer peptide Ac-LIVAGKC (LK 6 C) and afterwards cysteine-mediated disulfide bonds were introduced to the nanofibers assembled from the hexamer. The bioactive RGD motif visibly supported (e) Transmission electron microscopy and (f) atomic force microscopy images of reduced graphene dispersions at pH 2 with a 1 : 8 graphene-amyloid fibril ratio demonstrating the formation of stable amyloid-graphene films that can remain conjugated and stable for several weeks.…”

Section: -151mentioning

confidence: 99%

“…Overall, this suggests new pathways for cell culture and tissue engineering by jointly exploring the 3D patterns created by different amyloidogenic peptides and the ability to functionalize them with several biologically relevant molecules (adapted with permission). 165 modify gelation kinetics in self-assembling systems without disrupting bioactivity is an important aspect for the development of injectable therapies in regenerative medicine. Feasible strategies for novel therapeutic approaches using self-assembling peptide nanofibers for angiogenesis and cardiac repair can be envisioned when reading the study of Lin et al, 2012.…”

Section: -151mentioning

confidence: 99%

Amyloid-based nanosensors and nanodevices

2014

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Self-assembling amyloid-like peptides and proteins give rise to promising biomaterials with potential applications in many fields. Amyloid structures are formed by the process of molecular recognition and self-assembly, wherein a peptide or protein monomer spontaneously self-associates into dimers and oligomers and subsequently into supramolecular aggregates, finally resulting in condensed fibrils. Mature amyloid fibrils possess a quasi-crystalline structure featuring a characteristic fiber diffraction pattern and have well-defined properties, in contrast to many amorphous protein aggregates that arise when proteins misfold. Core sequences of four to seven amino acids have been identified within natural amyloid proteins. They are capable to form amyloid fibers and fibrils and have been used as amyloid model structures, simplifying the investigations on amyloid structures due to their small size. Recent studies have highlighted the use of self-assembled amyloid-based fibers as nanomaterials. Here, we discuss the latest advances and the major challenges in developing amyloids for future applications in nanotechnology and nanomedicine, with the focus on development of sensors to study protein-ligand interactions.

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“…In that study, we evaluated a physical gel whose fibers depended solely on physical forces for self assembly. Consequently, when soaked in a large volume excess of water, the fibers can get diluted, causing the gel to lose its shape27. We have since optimized the original sequences and introduced cysteine-mediated disulfide crosslinks into our rational peptide design27.…”

mentioning

confidence: 99%

“…Consequently, when soaked in a large volume excess of water, the fibers can get diluted, causing the gel to lose its shape27. We have since optimized the original sequences and introduced cysteine-mediated disulfide crosslinks into our rational peptide design27. As a result, the gels attained significantly greater stiffness, elasticity and shape fidelity even after a prolonged period of water immersion27.…”

mentioning

confidence: 99%

Transparent crosslinked ultrashort peptide hydrogel dressing with high shape-fidelity accelerates healing of full-thickness excision wounds

Seow

Salgado

Lane

et al. 2016

Sci Rep

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Wound healing is a major burden of healthcare systems worldwide and hydrogel dressings offer a moist environment conducive to healing. We describe cysteine-containing ultrashort peptides that self-assemble spontaneously into hydrogels. After disulfide crosslinking, the optically-transparent hydrogels became significantly stiffer and exhibited high shape fidelity. The peptide sequence (LIVAGKC or LK6C) was then chosen for evaluation on mice with full-thickness excision wounds. Crosslinked LK6C hydrogels are handled easily with forceps during surgical procedures and offer an improvement over our earlier study of a non-crosslinked peptide hydrogel for burn wounds. LK6C showed low allergenic potential and failed to provoke any sensitivity when administered to guinea pigs in the Magnusson-Kligman maximization test. When applied topically as a dressing, the medium-infused LK6C hydrogel accelerated re-epithelialization compared to controls. The peptide hydrogel is thus safe for topical application and promotes a superior rate and quality of wound healing.

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Tunable Mechanical Properties of Ultrasmall Peptide Hydrogels by Crosslinking and Functionalization to Achieve the 3D Distribution of Cells

Cited by 37 publications

References 33 publications

De Novo Design and Experimental Characterization of Ultrashort Self-Associating Peptides

De Novo Design and Experimental Characterization of Ultrashort Self-Associating Peptides

Amyloid-based nanosensors and nanodevices

Transparent crosslinked ultrashort peptide hydrogel dressing with high shape-fidelity accelerates healing of full-thickness excision wounds

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