Dynamic protein hydrogels with reversibly tunable stiffness regulate human lung fibroblast spreading reversibly

Fu, Linglan; Haage, Amanda; Kong, Na; Tanentzapf, Guy; Li, Hongbin

doi:10.1039/c9cc01276a

Cited by 37 publications

(44 citation statements)

References 34 publications

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“…For example, one study has shown that hepatic stellate cells cultured on active MeHA hydrogel substrates respond to dynamic changes in matrix stiffness (20-fold) by spreading, changing actin fiber organization to form stress fibers of α-smooth muscle actin (α-SMA), and increasing nuclear YAP content, all indicative of myofibroblast differentiation [43]. Similar observations have been made using other active biomaterials [36], [59], [66], [77], [78], [135]. In contrast, matrix softening was reported to induce valvular myofibroblast de-activation [31].…”

Section: Manipulation Of Mechanotransduction Associated With Cell-endogenous Forcesmentioning

confidence: 64%

“…Similarly, a four-fold increase of stiffness was observed in DNA crosslinked polyacrylamide substrates [77]. Reversible stiffening over several cycles was demonstrated in dynamic protein hydrogels that undergo secondary crosslinking between tyrosine residues due to redox reactions [78], or tyrosinase enzyme [79], [80]. In contrast, sortase enzyme mediated crosslinking led to reversible stiffening in PEG-peptide hydrogels [81].…”

Section: Chemical Control Of Matrix Structurementioning

confidence: 92%

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Active biomaterials for mechanobiology

Özkale

Sakar²,

Mooney

2021

Biomaterials

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Active biomaterials offer novel approaches to study mechanotransduction in mammalian cells. These material systems can either modulate the resistance cells sense to endogenous forces or apply exogenous forces on cells in a temporally controlled manner. The ability to dynamically control the mechanical cues cells receive allows one to mimic various aspects of the native microenvironment. The implementation of active biomaterials in mechanobiology has generated valuable insight relevant to a variety of biological processes including but not limited to stem cell lineage commitment, disease progression, and tissue regeneration. The field is rapidly evolving as emerging technologies and materials are introduced and will continue to develop in the near future.

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Section: Manipulation Of Mechanotransduction Associated With Cell-endogenous Forcesmentioning

confidence: 64%

Section: Chemical Control Of Matrix Structurementioning

confidence: 92%

Active biomaterials for mechanobiology

Özkale

Sakar²,

Mooney

2021

Biomaterials

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“…Adapted with permission. [ 72 ] Copyright 2019, Royal Society of Chemistry. D) Self‐healing protein hydrogels constructed by crosslinking SAE proteins with mechanically stable noncovalent ligand–receptor interactions.…”

Section: Protein Mechanics Has Made It Possible To Engineer Protein‐based Biomaterials To Mimic the Passive Elastic Properties Of Musclesmentioning

confidence: 99%

“…Using a redox‐controlled mutually exclusive protein, which behaves as a redox‐controlled protein folding switch, we engineered dynamic protein hydrogels that can change their Young's modulus in response to redox potential. [ 58,72,73 ] The Young's modulus of the hydrogel can be switched between a lower and a higher value, which differ by 2–4 times, by redox potential in a fully reversible fashion (Figure 4C). Liu et al used a Ca 2+ ‐responsive RTX protein, which folds into a Ca 2+ ‐loaded β‐roll structure in the presence of Ca 2+ and behaves as a random coil in the absence of Ca 2+ , to construct Ca 2+ ‐responsive protein hydrogels.…”

Section: A Diverse Range Of Sae Proteins For Constructing Protein Hydrogels: Imparting Novel Properties To Protein Hydrogelsmentioning

confidence: 99%

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There Is Plenty of Room in The Folded Globular Proteins: Tandem Modular Elastomeric Proteins Offer New Opportunities in Engineering Protein‐Based Biomaterials

2021

Advanced NanoBiomed Research

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Shock absorber‐like elastomeric (SAE) proteins have become attractive building blocks to engineer protein hydrogels with tailored mechanical properties. These elastomeric proteins are tandem modular proteins consisting of individually folded globular domains and exhibit distinct mechanical properties. In response to stretching, folded globular domains can undergo force‐induced unfolding, leading to a significant change in protein stiffness and energy dissipation. These molecular behaviors of individual proteins can be harnessed and translated into macroscopic mechanical traits of protein hydrogels when such SAE proteins are used as building blocks to engineer protein hydrogels. These SAE proteins offer unique opportunities to rationally design protein‐based hydrogels by programming the mechanical properties of individual proteins at the molecular level, and thus help bridge the gap between biomechanics of macroscopic biomaterials and nanomechanics of single molecules.

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Calmodulin‐Based Dynamic Protein Hydrogels with Three Distinct Mechanical Stiffness

Bian,

Kong,

Arslan

et al. 2024

Adv Funct Materials

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Stimuli‐responsive hydrogels that leverage protein conformational changes are of significant interest in the design of dynamic materials applicable in a myriad of fields, such as drug delivery, actuators, biosensors, and microfluidics. The small calcium binding protein calmodulin (CaM), which undergoes three‐stage conformational changes upon successive binding with Ca2+ and specific ligands, offers a mechanism to create dynamic hydrogels with three distinct physical states. In this work, a CaM‐based recombinant protein hydrogel is engineered using [Ru(bpy)3]2+‐mediated photo‐crosslinking. This hydrogel displays the ability to reversibly increase its Young's modulus by 1.5‐fold and ∼7‐fold, respectively, upon binding with Ca2+ and subsequent interaction with trifluoperazine. The magnitude of stiffness changes is tunable by adjusting the length proportion of dynamic and static domains and modifying protein content. This tunable and reversible control over hydrogel mechanics is further utilized to engineer shape‐morphing materials, highlighting the versatile potential of this CaM‐based protein hydrogel for diverse applications.

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Dynamic protein hydrogels with reversibly tunable stiffness regulate human lung fibroblast spreading reversibly

Abstract: Fibroblast cells change their morphology reversibly in response to changes in protein hydrogel stiffness.

Cited by 37 publications

References 34 publications

Active biomaterials for mechanobiology

Active biomaterials for mechanobiology

There Is Plenty of Room in The Folded Globular Proteins: Tandem Modular Elastomeric Proteins Offer New Opportunities in Engineering Protein‐Based Biomaterials

Calmodulin‐Based Dynamic Protein Hydrogels with Three Distinct Mechanical Stiffness

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