Forced protein unfolding leads to highly elastic and tough protein hydrogels

Abstract

Protein-based hydrogels usually do not exhibit high stretchability or toughness, significantly limiting the scope of their potential biomedical applications. Here we report the engineering of a chemically crosslinked, highly elastic and tough protein hydrogel using a mechanically extremely labile, de novo designed protein that assumes the classical ferredoxin-like fold structure. Due to the low mechanical stability of the ferredoxin-like fold structure, swelling of hydrogels causes a significant fraction of the fold structure domains to unfold. Subsequent collapse and aggregation of unfolded ferredoxin-like fold structure domains leads to intertwining of physically and chemically crosslinked networks, entailing hydrogels with unusual physical and mechanical properties: a negative swelling ratio, high stretchability and toughness. These hydrogels can withstand an average strain of 450% before breaking and show massive energy dissipation. Upon relaxation, refolding of the ferredoxin-like fold structure domains enables the hydrogel to recover its massive hysteresis. This novel biomaterial may expand the scope of hydrogel applications in tissue engineering.

Rationally Designed Dynamic Protein Hydrogels with Reversibly Tunable Mechanical Properties

“…[28][29][30][31][32][33] By chemically denaturing the folded globular domains using chemical denaturants, we showed that it is possible to decrease the Young's modulus of tandem modular protein-based hydrogels. [ 29,31 ] However, for any potential biological applications, biologically compatible and mild conditions are required. Here, we propose incorporating protein-folding switches into tandem modular proteins towards constructing protein hydrogels to achieve dynamic mechanical properties regulation.…”

The physics of pulling polyproteins: a review of single molecule force spectroscopy using the AFM to study protein unfolding

“…These proteins are being exploited as building blocks for biological materials that exhibit attractive and bespoke mechanical properties, as they possess the desired elasticity, mechanical strength and resilience required for these functional materials. Recent studies have demonstrated examples of engineered elastomeric proteins with mechanical properties that mimic and surpass those of natural elastomeric proteins, and have utilised natural elastomeric proteins that are well-characterised on the nano-scale to engineer hydrogels with specific macro-scale mechanical properties [240][241][242][243]. Central to these novel developments is the ability to measure the mechanical properties of the building block, the protein.…”

Quantifying thiol–gold interactions towards the efficient strength control

“…These interactions are unbinding forces that originated from specific interactions in biological systems (that is, the unfolding of proteins, melting of DNA strands, antigen-antibody interactions, ligand-receptor interactions and protein-nucleic acid interactions), entropic elasticity, basic supramolecular interactions (that is, hydrogen bonds, coordinated bonds, p-p interactions, hydrophobic interactions and so on) and even the strength of a single covalent bond 13,[17][18][19][20][21][22][23][24][25][26][27][28] . The investigations of molecular interactions in complicated systems, such as on live bacterial surfaces, in intact virus particle, and in condensed polymer materials, have also been performed successfully via AFM-based SMFS 21,22,29 .…”