Towards constructing extracellular matrix-mimetic hydrogels: An elastic hydrogel constructed from tandem modular proteins containing tenascin FnIII domains

Lv, Shanshan; Bu, Tianjia; Kayser, Jona; Bausch, Andreas R.; Li, Hongbin

doi:10.1016/j.actbio.2013.01.002

Cited by 45 publications

(52 citation statements)

References 53 publications

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“…It is of note that (I27-G N -I27) 4 and (I27 3 -G C ) 3 contain different number of I27 domains, ensuring that the two proteins are not complementary in structure and will not form dimers after the association of G N and G C fragments. [ 10,35 ] As expected, we found that mixing aqueous solutions of 10% (m/v) (I27-G N -I27) 4 and 10% (I27 3 -G C ) 3 readily leads to the formation of a transparent solid hydrogel ( Figure 3 A). By contrast, an aqueous solution of (I27-G N -I27) 4 or (I27 3 -G C ) 3 alone does not form hydrogels, even at concentrations greater than 10%.…”

Section: Fragment Reconstitution Can Serve As a Driving Force To Desisupporting

confidence: 58%

“…To demonstrate the feasibility of this design, we employed a two-component approach, [ 18,35 ] where two proteins (I27-G N -I27) 4 and (I27 3 -G C ) 3 were engineered and used as building blocks in hydrogel construction (Figure 1 B). These two proteins can be considered as tetra-and trifunctional, where the reconstitution between G N and G C in the two proteins should result in the crosslinking of (I27-G N -I27) 4 and (I27 3 -G C ) 3 , leading to the formation of a network structure when the protein concentrations are high enough.…”

Section: Fragment Reconstitution Can Serve As a Driving Force To Desimentioning

confidence: 99%

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Protein Fragment Reconstitution as a Driving Force for Self‐Assembling Reversible Protein Hydrogels

Kong

2015

Adv Funct Materials

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Due to their potential biomedical applications, protein-based hydrogels have attracted considerable interest. Although various methods have been developed to engineer self-assembling, physically-crosslinked protein hydrogels, exploring novel driving forces to engineer such hydrogels remains challenging. Protein fragment reconstitution, also known as fragment complementation, is a self-assembling mechanism by which protein fragments can reconstitute the folded conformation of the native protein when split into two halves. Although it has been used in biophysical studies and bioassays, fragment reconstitution has not been explored for hydrogel construction. Using a small protein GL5 as a model, which is capable of fragment reconstitution to reconstitute the folded GL5 spontaneously when split into two halves, GN and GC, we demonstrate that protein fragment reconstitution is a novel driving force for engineering self-assembling reversible protein hydrogels. Fragment reconstitution between GN and GC crosslinks GN and GC-containing proteins into self-assembling reversible protein hydrogels. These novel hydrogels show temperature-dependent reversible sol-gel transition, and excellent property against erosion in water. Since many proteins can undergo fragment reconstitution, we anticipate that such fragment reconstitution may offer a general driving force for engineering protein hydrogels from a variety of proteins, and thus signifi cantly expanding the 'toolbox' currently available in the fi eld of biomaterials. DOI IntroductionProtein hydrogels have attracted considerable interest over the last two decades due to their potential applications in a wide range of biomedical applications, including drug delivery, as artifi cial extracellular matricies and regenerative medicines. [1][2][3] Among engineered protein hydrogels, self-assembling hydrogels are of particular interest. [ 2,4,5 ] Inspired by the pioneering work of Tirrell and co-workers, [ 6 ] researchers have been developing novel strategies for engineering self-assembling protein hydrogels [4][5][6][7][8] Adv. Funct explored in engineering self-assembling protein hydrogels or supramolecular protein polymers. For the two split fragments A and B that can undergo fragment reconstitution to reconstitute the native folded structure, it should be feasible to crosslink multifunctional polymers (S-A) n and (S-B) m into a polymer network and form a hydrogel, where S represents spacers, A and B are the two fragments capable of reconstituting, and m and n represent the number of repeating units (Figure 1 B). Using fragments from a loop elongation variant of GB1 as a model system, we demonstrate the proof-of-principle of using protein fragment reconstitution as a driving force to engineer self-assembling protein hydrogels. Using different protein designs, we demonstrate both two-component as well as singlecomponent approaches to engineer protein fragment reconstitution-driven protein hydrogels.

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Section: Fragment Reconstitution Can Serve As a Driving Force To Desisupporting

confidence: 58%

Section: Fragment Reconstitution Can Serve As a Driving Force To Desimentioning

confidence: 99%

Protein Fragment Reconstitution as a Driving Force for Self‐Assembling Reversible Protein Hydrogels

Kong

2015

Adv Funct Materials

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“…The malleability of a proteins and biomimetic polymers. Recent studies have shown examples of engineered elastomeric proteins with mechanical properties that mimic and surpass those of natural elastomeric proteins 27 , and have utilised natural elastomeric proteins that are well-characterised on the nano-scale to engineer hydrogels with 5 specific macro-scale mechanical properties 26 ( Figure 2A). Another study exploited the architecture found in spider silk 20 proteins to engineer materials with remarkable extensibility and strength 29 ( Figure 2B).…”

Section: Introductionmentioning

confidence: 99%

Towards design principles for determining the mechanical stability of proteins

Hoffmann

Tych

Hughes

et al. 2013

Phys. Chem. Chem. Phys.

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The successful integration of proteins into bionanomaterials with specific and desired function requires an accurate understanding of their material properties. Two such important properties are their mechanical stability and malleability. While single molecule manipulation techniques 15 now routinely provide access to these, there is a need to move towards predictive tools that can rationally identify proteins with desired material properties. We provide a comprehensive review of the available experimental data on the single molecule characterisation of proteins using the 20 atomic force microscope. We uncover a number of empirical relationships between the measured mechanical stability of a protein and its malleability which provide a set of simple tools which might be employed to estimate properties of previously uncharacterised proteins. 25

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“…Fibronectin type III domains of TNC have been incorporated into elastic hydrogels as binding sites for cells to mimic the in vivo architecture (Lv et al, 2013). The domains from TNC promoted cell adhesion and spreading in these hydrogels, which could be tuned to have varying mechanical properties (Lv et al, 2013).…”

Section: Matricellular Proteinsmentioning

confidence: 99%

“…The domains from TNC promoted cell adhesion and spreading in these hydrogels, which could be tuned to have varying mechanical properties (Lv et al, 2013). Another group modified polyamide electrospun nanofibers to display tenascin-C peptides for neuronal cell culture (Ahmed et al, 2005).…”

Section: Matricellular Proteinsmentioning

confidence: 99%

Matricellular proteins and biomaterials

Morris

Kyriakides

2014

Matrix Biology

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Biomaterials are essential to modern medicine as components of reconstructive implants, implantable sensors, and vehicles for localized drug delivery. Advances in biomaterials have led to progression from simply making implants that are nontoxic to making implants that are specifically designed to elicit particular functions within the host. The interaction of implants and the extracellular matrix during the foreign body response is a growing area of concern for the field of biomaterials, because it can lead to implant failure. Expression of matricellular proteins is modulated during the foreign body response and these proteins interact with biomaterials. The design of biomaterials to specifically alter the levels of matricellular proteins surrounding implants provides a new avenue for the design and fabrication of biomimetic biomaterials.

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Towards constructing extracellular matrix-mimetic hydrogels: An elastic hydrogel constructed from tandem modular proteins containing tenascin FnIII domains

Cited by 45 publications

References 53 publications

Protein Fragment Reconstitution as a Driving Force for Self‐Assembling Reversible Protein Hydrogels

Protein Fragment Reconstitution as a Driving Force for Self‐Assembling Reversible Protein Hydrogels

Towards design principles for determining the mechanical stability of proteins

Matricellular proteins and biomaterials

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