Tuning of hydrogel stiffness using a two‐component peptide system for mammalian cell culture

Scelsi, Alessandra; Bochicchio, Brigida; Smith, Andrew M.; Workman, Victoria L.; Díaz, L.; Saiani, Alberto; Pepe, Antonietta

doi:10.1002/jbm.a.36568

Cited by 34 publications

(24 citation statements)

References 64 publications

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“…Moreover, efforts have been made to improve the mechanical properties of established supramolecular peptide-based gels, focusing mainly in developing methods to enhance the mechanical rigidity of the gel, as these gels are typically only moderately stiff (Yan and Pochan, 2010;Li et al, 2014). Such efforts include, among others, the introduction of crosslinks into the gel network (Hu et al, 2019) using physical (Greenfield et al, 2010;DiMaio et al, 2017;Bairagi et al, 2019;Scelsi et al, 2019), enzymatic (Bakota et al, 2011;Li et al, 2013), or chemical (Seow and Hauser, 2013;Khalily et al, 2015) crosslinking mechanisms. Interestingly, only limited success has been reported for chemical crosslinking of peptide-based gels (Li et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

Utilizing Frémy's Salt to Increase the Mechanical Rigidity of Supramolecular Peptide-Based Gel Networks

Fichman

2021

Front. Bioeng. Biotechnol.

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Peptide-based supramolecular gels are an important class of biomaterials that can be used for biomedical applications ranging from drug delivery to tissue engineering. Methodology that allows one to readily modulate the mechanical properties of these gels will allow yet even a broader range of applications. Frémy's salt is an inorganic salt and long-lived free radical that is known to oxidize phenols. Herein, we show that Frémy's salt can be used to dramatically increase the mechanical rigidity of hydrogels formed by tyrosine-containing self-assembling β-hairpin peptides. When Frémy's salt is added to pre-formed gels, it converts tyrosine residues to o-quinones that can subsequently react with amines present within the lysine side chains of the assembled peptide. This results in the installation of chemical crosslinks that reinforce the gel matrix. We characterized the unoxidized and oxidized gel systems using UV-Vis, transmission electron microscopy and rheological measurements and show that Frémy's salt increases the gel rigidity by nearly one order of magnitude, while retaining the gel's shear-thin/recovery behavior. Thus, Frémy's salt represents an on-demand method to modulate the mechanical rigidity of peptide-based self-assembled gels.

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Section: Introductionmentioning

confidence: 99%

Utilizing Frémy's Salt to Increase the Mechanical Rigidity of Supramolecular Peptide-Based Gel Networks

Fichman

2021

Front. Bioeng. Biotechnol.

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“…With increasing concentration, the gel strength tends to increase from 0.4 kPa at 0.1% L1 to 20 kPa at 1% L1 concentration (Figures 3a and S3a). 59 In a solution, there is always a competition between Brownian motion and intermolecular interactions. Moreover, the higher numbers of interacting sites were available for a fixed concentration of peptides by increasing protein concentration in the solution.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

Triggering Supramolecular Hydrogelation Using a Protein–Peptide Coassembly Approach

2020

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In recent years, the molecular self-assembly approach has witnessed a sudden surge in coassembly strategy to achieve extensive control over accessing diverse nanostructures and functions. To this direction, peptide–peptide coassembly has been explored to some extent in the literature, but protein–peptide coassembly is still in its infancy for controlling the self-assembling properties. To the best of our knowledge, our study illustrated the merits of protein–peptide coassembly toward inducing gelation to a nongelator dipeptide sequence, for the first time. This simplistic approach could provide access to diverse mechanical and structural properties within a single gelator domain at identical concentrations with a simple variation in the protein concentrations. Interestingly, the protein–peptide interactions could transform aggregate-like structures into fibrillar nanostructures. The study attempts to provide the proof of concept for the nonspecific protein–peptide interactions purely based on simple noncovalent interactions. The range of dissociation constants and binding energies obtained from bioloyer interferometry and docking studies confirmed the involvement of noncovalent interactions in protein–peptide coassembly, which triggers gelation. Moreover, different binding affinities of a protein toward an individual peptide essentially demonstrated a route to achieve precise control over differential self-assembling properties. Another important aspect of this study was entrapment of an enzyme protein within the gel network during coassembly without inhibiting enzyme activity, which can serve as a scaffold for catalytic reactions. The present study highlights the nonconventional way of protein–peptide interactions in triggering self-assembly in a nonassembling precursor. We anticipate that fundamental insights into the intermolecular interactions would lead to novel binary supramolecular hydrogels that can be developed as a next generation biomaterial for various biomedical applications.

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“…This design makes peptide hydrogels easy to tune and modify, as discrete changes in the amino acid sequence can yield hydrogels with a wide range of properties [41,119,120]. The control over the sequence also provides more degrees of freedom in the hydrogel design, thus, enabling the independent tuning of different parameters, including the mechanical and chemical properties, cell-matrix interactions and degradability.…”

Section: Polypeptidesmentioning

confidence: 99%

Self-Assembling Polypeptide Hydrogels as a Platform to Recapitulate the Tumor Microenvironment

Lachowski

Matellan

Cortés

et al. 2021

Cancers

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The tumor microenvironment plays a critical role in modulating cancer cell migration, metabolism, and malignancy, thus, highlighting the need to develop in vitro culture systems that can recapitulate its abnormal properties. While a variety of stiffness-tunable biomaterials, reviewed here, have been developed to mimic the rigidity of the tumor extracellular matrix, culture systems that can recapitulate the broader extracellular context of the tumor microenvironment (including pH and temperature) remain comparably unexplored, partially due to the difficulty in independently tuning these parameters. Here, we investigate a self-assembled polypeptide network hydrogel as a cell culture platform and demonstrate that the culture parameters, including the substrate stiffness, extracellular pH and temperature, can be independently controlled. We then use this biomaterial as a cell culture substrate to assess the effect of stiffness, pH and temperature on Suit2 cells, a pancreatic cancer cell line, and demonstrate that these microenvironmental factors can regulate two critical transcription factors in cancer: yes-associated protein 1 (YAP) and hypoxia inducible factor (HIF-1A).

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Tuning of hydrogel stiffness using a two‐component peptide system for mammalian cell culture

Cited by 34 publications

References 64 publications

Utilizing Frémy's Salt to Increase the Mechanical Rigidity of Supramolecular Peptide-Based Gel Networks

Utilizing Frémy's Salt to Increase the Mechanical Rigidity of Supramolecular Peptide-Based Gel Networks

Triggering Supramolecular Hydrogelation Using a Protein–Peptide Coassembly Approach

Self-Assembling Polypeptide Hydrogels as a Platform to Recapitulate the Tumor Microenvironment

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