Decorating protein hydrogels reversibly enables dynamic presentation and release of functional protein ligands on protein hydrogels

Wang, Ruidi; Fu, Linglan; Li, Hongbin

doi:10.1039/c9cc06374a

Cited by 12 publications

(11 citation statements)

References 40 publications

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“… 319 Similarly, in a 3D setting, the photo-responsive hydrogels also behaved as one of the most popular approaches for dynamically regulating the presence and removal of biological cues (e.g., RGD ligands) in a spatiotemporal-controlled manner. 320 , 321 DeForest et al developed a novel approach to selectively pattern protein vitronectin present within PEG-based 3D hydrogel, which, thereby, could spatially control the reversible differentiation of human MSCs (hMSCs) into osteoblasts with target gene expression. Especially, the photodeprotection-oxime-ligation sequence and ortho-nitrobenzyl ester photo-cleavage reaction within the hydrogel could bring about protein anchorage and removal, respectively.…”

Section: Influences Of Hydrogel Properties On Cell Behavior and Signaling Pathwaysmentioning

confidence: 99%

Current hydrogel advances in physicochemical and biological response-driven biomedical application diversity

Cao

Duan

Yan

et al. 2021

Sig Transduct Target Ther

480

256

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Hydrogel is a type of versatile platform with various biomedical applications after rational structure and functional design that leverages on material engineering to modulate its physicochemical properties (e.g., stiffness, pore size, viscoelasticity, microarchitecture, degradability, ligand presentation, stimulus-responsive properties, etc.) and influence cell signaling cascades and fate. In the past few decades, a plethora of pioneering studies have been implemented to explore the cell–hydrogel matrix interactions and figure out the underlying mechanisms, paving the way to the lab-to-clinic translation of hydrogel-based therapies. In this review, we first introduced the physicochemical properties of hydrogels and their fabrication approaches concisely. Subsequently, the comprehensive description and deep discussion were elucidated, wherein the influences of different hydrogels properties on cell behaviors and cellular signaling events were highlighted. These behaviors or events included integrin clustering, focal adhesion (FA) complex accumulation and activation, cytoskeleton rearrangement, protein cyto-nuclei shuttling and activation (e.g., Yes-associated protein (YAP), catenin, etc.), cellular compartment reorganization, gene expression, and further cell biology modulation (e.g., spreading, migration, proliferation, lineage commitment, etc.). Based on them, current in vitro and in vivo hydrogel applications that mainly covered diseases models, various cell delivery protocols for tissue regeneration and disease therapy, smart drug carrier, bioimaging, biosensor, and conductive wearable/implantable biodevices, etc. were further summarized and discussed. More significantly, the clinical translation potential and trials of hydrogels were presented, accompanied with which the remaining challenges and future perspectives in this field were emphasized. Collectively, the comprehensive and deep insights in this review will shed light on the design principles of new biomedical hydrogels to understand and modulate cellular processes, which are available for providing significant indications for future hydrogel design and serving for a broad range of biomedical applications.

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Section: Influences Of Hydrogel Properties On Cell Behavior and Signaling Pathwaysmentioning

confidence: 99%

Current hydrogel advances in physicochemical and biological response-driven biomedical application diversity

Cao

Duan

Yan

et al. 2021

Sig Transduct Target Ther

480

256

View full text Add to dashboard Cite

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“…Hydrogels can concomitantly respond to more than one stimulus. For instance, protein fragment reconstitution can be used to reversibly create and decorate a protein hydrogel responsive to both temperature and redox status [ 153 ].…”

Section: Smart Protein Hydrogelsmentioning

confidence: 99%

Protein Hydrogels: The Swiss Army Knife for Enhanced Mechanical and Bioactive Properties of Biomaterials

Huerta-López

Alegre-Cebollada

2021

Nanomaterials

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Biomaterials are dynamic tools with many applications: from the primitive use of bone and wood in the replacement of lost limbs and body parts, to the refined involvement of smart and responsive biomaterials in modern medicine and biomedical sciences. Hydrogels constitute a subtype of biomaterials built from water-swollen polymer networks. Their large water content and soft mechanical properties are highly similar to most biological tissues, making them ideal for tissue engineering and biomedical applications. The mechanical properties of hydrogels and their modulation have attracted a lot of attention from the field of mechanobiology. Protein-based hydrogels are becoming increasingly attractive due to their endless design options and array of functionalities, as well as their responsiveness to stimuli. Furthermore, just like the extracellular matrix, they are inherently viscoelastic in part due to mechanical unfolding/refolding transitions of folded protein domains. This review summarizes different natural and engineered protein hydrogels focusing on different strategies followed to modulate their mechanical properties. Applications of mechanically tunable protein-based hydrogels in drug delivery, tissue engineering and mechanobiology are discussed.

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“…They are usually physically cross-linked hydrogels, and interactions between peptides or protein domains are the main driving force for the self-assembly (Jonker et al 2012; Banta et al 2010; Kopecek and Yang 2012). The representative protein building blocks include coiled-coil (Petka 1998; Wang et al 1999; Jing et al 2008; Olsen et al 2018; Hill et al 2019), β-hairpin peptide (Collier et al 2001; Schneider et al 2002; Pochan et al 2003; Kretsinger et al 2005; Wu et al 2011; Yamada et al 2019;), silk fibrin (Kim et al 2004; Buitrago et al 2018), SpyCatcher-SpyTag (Lyu et al 2017; Wang et al 2017; Yang et al 2019; Wang et al 2019), WW domain-polyproline containing peptide (Maciasa et al2002; Foo et al 2009), and TIP-1:Kir complex (Guan et al 2013; Xu et al 2017; Wu et al 2018). Although nature may provide a large number of functional protein building blocks capable of forming hydrogels, only a small part of them has been discovered and explored.…”

Section: Introductionmentioning

confidence: 99%

A non-structural pure enzyme protein forms a LCST type of stimuli-responsive and reversible hydrogel with novel structure and catalytic activity

Nie

et al. 2021

Preprint

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Hydrogels have a wide range of applications such as in biomedicine, cosmetics and soft electronics. Compared to polymer hydrogels based on covalent bonding, protein hydrogels offer distinct advantages owing to their biocompatibility and better access to molecular engineering. However, pure and natural protein hydrogels have been seldom reported except for structural proteins like collagen and silk fibrin. Here, we report the unusual ability and mechanism of a unique natural enzyme, lipoate-protein ligase A (LplA) of E. coli to self-assemble into a stimuli-responsive and reversible hydrogel of the low critical solution temperature (LCST) type. This is the first globular and catalytic protein found to form a hydrogel in response to temperature, pH and the presence of ions. Protein structure based analysis reveals the key residues responsible for the gel formation and mutational studies confirms the essential roles of hydrogen bonding between the C-terminal domains and electrostatic interactions in the N-terminal domains. Characterization of phase transitions of wild type LplA and its mutants using small angle X-ray scattering (SAXS) yields details of the gelation process from initial dimer formation over a pre-gel-state to full network development. Further electron microscopic analyses and modeling of SAXS data suggest an unusual interlinked ladder-like structure of the macroscopic crosslinking network with dimers as ladder steps. The unique features of this first reported protein hydrogel may open up hitherto inaccessible applications, especially those taking advantage of the inherent catalytic activity of LplA.

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Decorating protein hydrogels reversibly enables dynamic presentation and release of functional protein ligands on protein hydrogels

Abstract: Utilizing protein fragment reconstitution, we demonstrate the reversible and repeatable functionalization of protein hydrogels.

Cited by 12 publications

References 40 publications

Current hydrogel advances in physicochemical and biological response-driven biomedical application diversity

Current hydrogel advances in physicochemical and biological response-driven biomedical application diversity

Protein Hydrogels: The Swiss Army Knife for Enhanced Mechanical and Bioactive Properties of Biomaterials

A non-structural pure enzyme protein forms a LCST type of stimuli-responsive and reversible hydrogel with novel structure and catalytic activity

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