Rational design and application of responsive α-helical peptide hydrogels

Banwell, Eleanor F.; Abelardo, Edgardo; Adams, Dave J.; Birchall, Martin A.; Corrigan, Adam; Donald, Athene M.; Kirkland, Mark; Serpell, Louise C.; Butler, Michael F.; Woolfson, Derek N.

doi:10.1038/nmat2479

Cited by 440 publications

(421 citation statements)

References 30 publications

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“…The increasing knowledge about sequence-to-structure relationships has facilitated design of peptides that adopt well-defined structural motifs, such as coiled coils, helix-loop-helices and beta-hairpins and have enabled development of self-assembling peptide fibers, tapes, nanoparticles, and hydrogels. [7][8][9][10][11][12][13] Furthermore, by connecting two or more peptide using short linkers, fairly complex assembled structures can be formed as result of the well-defined folding pattern of each single peptide folding motif. [14][15][16][17][18] Peptides have also been conjugated to larger synthetic polymeric backbones, such as poly(ethylene glycol) (PEG), in order to create a wider range of supramolecular hybrid materials and nanostructures, [19][20][21] including peptide-polymer hybrid hydrogels, fibrils, spherulities and micells.…”

Section: Introductionmentioning

confidence: 99%

Tailoring Supramolecular Peptide–Poly(ethylene glycol) Hydrogels by Coiled Coil Self-Assembly and Self-Sorting

2016

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Physical hydrogels are extensively used in a wide range of biomedical applications. However, different applications require hydrogels with different mechanical and structural properties.Tailoring these properties demands exquisite control over the supramolecular interactions involved. Here we show that it is possible to control the mechanical properties of hydrogels using de novo designed coiled coil peptides with different affinities for dimerization. Four different non-orthogonal peptides, designed to fold into four different coiled coil heterodimers with dissociation constants spanning from µM to pM, were conjugated to star-shaped 4-armpoly(ethylene glycol) (PEG). The different PEG-coiled coil conjugates self-assemble as a result of peptide heterodimerization. Different combinations of PEG-peptide conjugates assemble into PEG-peptide networks and hydrogels with distinctly different thermal stabilities, supramolecular and rheological properties, reflecting the peptide dimer affinities. We also demonstrate that it is possible to rationally modulate the self-assembly process by means of thermodynamic self-sorting by sequential additions of non-pegylated peptides. The specific interactions involved in peptide dimerization thus provides means for programmable and reversible self-assembly of hydrogels with precise control over rheological properties, which 2 can significantly facilitate optimization of their overall performance and adaption to different processing requirements and applications.

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Section: Introductionmentioning

confidence: 99%

Tailoring Supramolecular Peptide–Poly(ethylene glycol) Hydrogels by Coiled Coil Self-Assembly and Self-Sorting

2016

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“…A number of molecular designs have been developed for the synthesis of self‐assembling peptide LMWHs with the four main families being amphiphilic peptides, 13, 14, 15 short peptide derivatives, 16, 17, 18, 19, 20 α ‐helix/coil‐coil peptides 21, 22 and β ‐sheet peptides. 4, 23, 24, 25, 26, 27, 28, 29 β ‐sheet peptides are of particular interest as they allow the fabrication of very stable hydrogels with properties that can be tailored through peptide design, media properties and processing.…”

Section: Introductionmentioning

confidence: 99%

Peptide hydrogel in vitro non‐inflammatory potential

Markey

Workman

Bruce

et al. 2016

Journal of Peptide Science

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Peptide‐based hydrogels have attracted significant interest in recent years as these soft, highly hydrated materials can be engineered to mimic the cell niche with significant potential applications in the biomedical field. Their potential use in vivo in particular is dependent on their biocompatibility, including their potential to cause an inflammatory response. In this work, we investigated in vitro the inflammatory potential of a β‐sheet forming peptide (FEFEFKFK; F: phenylalanine, E: glutamic acid; K: lysine) hydrogel by encapsulating murine monocytes within it (3D culture) and using the production of cytokines, IL‐β, IL‐6 and TNFα, as markers of inflammatory response. No statistically significant release of cytokines in our test sample (media + gel + cells) was observed after 48 or 72 h of culture showing that our hydrogels do not incite a pro‐inflammatory response in vitro. These results show the potential biocompatibility of these hydrogels and therefore their potential for in vivo use. The work also highlighted the difference in monocyte behaviour, proliferation and morphology changes when cultured in 2D vs. 3D. © 2016 The Authors Journal of Peptide Science published by European Peptide Society and John Wiley & Sons Ltd.

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“…This result agrees well with the experiments showing that hSAF QQQ formed β-sheet containing structures. 46 …”

Section: Cc-by-ncmentioning

confidence: 99%

The AWSEM-Amylometer: predicting amyloid propensity and fibril topology using an optimized folding landscape model

Chen

Schafer

Zheng

et al. 2017

Preprint

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Amyloids are fibrillar protein aggregates with simple repeated structural motifs in their cores, usually β-strands but sometimes α-helices. Identifying the amyloid-prone regions within protein sequences is important both for understanding the mechanisms of amyloid-associated diseases and for understanding functional amyloids. Based on the crystal structures of seven cross-β amyloidogenic peptides with different topologies and one recently solved cross-α fiber structure, we have developed a computational approach for identifying amyloidogenic segments in protein sequences using the 4.0 International license peer-reviewed) is the author/funder. It is made available under aThe copyright holder for this preprint (which was not . http://dx.doi.org/10.1101/138842 doi: bioRxiv preprint first posted online May. 17, 2017; aggregation-prone sequences in multiple datasets. The method also predicts the specific topologies (the relative arrangement of β-strands in the core) of the amyloid fibrilswell. An important advantage of the AWSEM-Amylometer over other existing methods is its direct connection with an efficient, optimized protein folding simulation model, AWSEM. This connection allows one to combine efficient and accurate search of protein sequences for amyloidogenic segments with the detailed study of the thermodynamic and kinetic roles that these segments play in folding and aggregation in the context of the entire protein sequence. We present new simulation results that highlight the free energy landscapes of peptides that can take on multiple fibril topologies. We also demonstrate how the Amylometer methodology can be straightforwardly extended to the study of functional amyloids that have the recently discovered cross-α fibril architecture.

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Rational design and application of responsive α-helical peptide hydrogels

Cited by 440 publications

References 30 publications

Tailoring Supramolecular Peptide–Poly(ethylene glycol) Hydrogels by Coiled Coil Self-Assembly and Self-Sorting

Tailoring Supramolecular Peptide–Poly(ethylene glycol) Hydrogels by Coiled Coil Self-Assembly and Self-Sorting

Peptide hydrogel in vitro non‐inflammatory potential

The AWSEM-Amylometer: predicting amyloid propensity and fibril topology using an optimized folding landscape model

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