It is a challenge to synthesize materials that possess the properties of biological muscles-strong, elastic and capable of self-healing. Herein we report a network of poly(dimethylsiloxane) polymer chains crosslinked by coordination complexes that combines high stretchability, high dielectric strength, autonomous self-healing and mechanical actuation. The healing process can take place at a temperature as low as -20 °C and is not significantly affected by surface ageing and moisture. The crosslinking complexes used consist of 2,6-pyridinedicarboxamide ligands that coordinate to Fe(III) centres through three different interactions: a strong pyridyl-iron one, and two weaker carboxamido-iron ones through both the nitrogen and oxygen atoms of the carboxamide groups. As a result, the iron-ligand bonds can readily break and re-form while the iron centres still remain attached to the ligands through the stronger interaction with the pyridyl ring, which enables reversible unfolding and refolding of the chains. We hypothesize that this behaviour supports the high stretchability and self-healing capability of the material.
The passive elasticity of muscle is largely governed by the I-band part of the giant muscle protein titin, a complex molecular spring composed of a series of individually folded immunoglobulin-like domains as well as largely unstructured unique sequences. These mechanical elements have distinct mechanical properties, and when combined, they provide the desired passive elastic properties of muscle, which are a unique combination of strength, extensibility and resilience. Single-molecule atomic force microscopy (AFM) studies demonstrated that the macroscopic behaviour of titin in intact myofibrils can be reconstituted by combining the mechanical properties of these mechanical elements measured at the single-molecule level. Here we report artificial elastomeric proteins that mimic the molecular architecture of titin through the combination of well-characterized protein domains GB1 and resilin. We show that these artificial elastomeric proteins can be photochemically crosslinked and cast into solid biomaterials. These biomaterials behave as rubber-like materials showing high resilience at low strain and as shock-absorber-like materials at high strain by effectively dissipating energy. These properties are comparable to the passive elastic properties of muscles within the physiological range of sarcomere length and so these materials represent a new muscle-mimetic biomaterial. The mechanical properties of these biomaterials can be fine-tuned by adjusting the composition of the elastomeric proteins, providing the opportunity to develop biomaterials that are mimetic of different types of muscles. We anticipate that these biomaterials will find applications in tissue engineering as scaffold and matrix for artificial muscles.
Naturally occurring elastomeric proteins function as molecular springs in their biological settings and show mechanical properties that underlie the elasticity of natural adhesives, cell adhesion proteins and muscle proteins. Constantly subject to repeated stretching-relaxation cycles, many elastomeric proteins demonstrate remarkable consistency and reliability in their mechanical performance. Such properties had hitherto been observed only in naturally evolved elastomeric proteins. Here we use single-molecule atomic force microscopy techniques to demonstrate that an artificial polyprotein made of tandem repeats of non-mechanical protein GB1 has mechanical properties that are comparable or superior to those of known elastomeric proteins. In addition to its mechanical stability, we show that GB1 polyprotein shows a unique combination of mechanical features, including the fastest folding kinetics measured so far for a tethered protein, high folding fidelity, low mechanical fatigue during repeated stretching-relaxation cycles and ability to fold against residual forces. These fine features make GB1 polyprotein an ideal artificial protein-based molecular spring that could function in a challenging working environment requiring repeated stretching-relaxation. This study represents a key step towards engineering artificial molecular springs with tailored nanomechanical properties for bottom-up construction of new devices and materials.
Designing synthetic protein hydrogels with tailored mechanical properties similar to naturally occurring tissues is an eternal pursuit in tissue engineering and stem cell and cancer research. However, it remains challenging to correlate the mechanical properties of protein hydrogels with the nanomechanics of individual building blocks. Here we use single-molecule force spectroscopy, protein engineering and theoretical modeling to prove that the mechanical properties of protein hydrogels are predictable based on the mechanical hierarchy of the cross-linkers and the load-bearing modules at the molecular level. These findings provide a framework for rationally designing protein hydrogels with independently tunable elasticity, extensibility, toughness and self-healing. Using this principle, we demonstrate the engineering of self-healable muscle-mimicking hydrogels that can significantly dissipate energy through protein unfolding. We expect that this principle can be generalized for the construction of protein hydrogels with customized mechanical properties for biomedical applications.
It is recognized that shear topology of two directly connected force-bearing terminal -strands is a common feature among the vast majority of mechanically stable proteins known so far. However, these proteins belong to only two distinct protein folds, Ig-like  sandwich fold and -grasp fold, significantly hindering delineating molecular determinants of mechanical stability and rational tuning of mechanical properties. Here we combine singlemolecule atomic force microscopy and steered molecular dynamics simulation to reveal that the de novo designed Top7 fold [Kuhlman B, Dantas G, Ireton GC, Varani G, Stoddard BL, Baker D (2003) Science 302:1364 -1368] represents a mechanically stable protein fold that is distinct from Ig-like  sandwich and -grasp folds. Although the two force-bearing  strands of Top7 are not directly connected, Top7 displays significant mechanical stability, demonstrating that the direct connectivity of force-bearing  strands in shear topology is not mandatory for mechanical stability. This finding broadens our understanding of the design of mechanically stable proteins and expands the protein fold space where mechanically stable proteins can be screened. Moreover, our results revealed a substructure-sliding mechanism for the mechanical unfolding of Top7 and the existence of two possible unfolding pathways with different height of energy barrier. Such insights enabled us to rationally tune the mechanical stability of Top7 by redesigning its mechanical unfolding pathway. Our study demonstrates that computational biology methods (including de novo design) offer great potential for designing proteins of defined topology to achieve significant and tunable mechanical properties in a rational and systematic fashion.atomic force microscopy ͉ computational design ͉ mechanical unfolding ͉ unfolding pathway P rotein mechanics is an important aspect of biology. Many proteins have evolved to sense, generate and bear mechanical forces (1) in a variety of biological processes, such as cellular adhesion (2), muscle contraction (3), and ligand-receptor interactions (4). Elastomeric proteins constitute a unique class of mechanical proteins with diverse functions ranging from molecular springs to structural materials of superb mechanical properties. Recent development in single-molecule force spectroscopy has made it possible to study the mechanical properties of proteins at singlemolecule level (5, 6). These studies not only revealed rich information about the architectural design of elastomeric proteins and shed light on the biophysical principles underpinning various biological processes, but also revealed promising prospect of using engineered elastomeric proteins for nanomechanical applications (7-9). However, in comparison to chemical and thermodynamic properties of proteins, experimental data on mechanical properties of proteins remains rather limited and molecular determinants of mechanical properties of proteins are less well understood. These factors have made it difficult or impossible to predict...
Most natural biomolecules may exist in either of two enantiomeric forms. Although in nature, amino acid biopolymers are characterized by l-type homochirality, incorporation of d-amino acids in the design of self-assembling peptide motifs has been shown to significantly alter enzyme stability, conformation, self-assembly behavior, cytotoxicity, and even therapeutic activity. However, while functional metabolite assemblies are ubiquitous throughout nature and play numerous important roles including physiological, structural, or catalytic functions, the effect of chirality on the self-assembly nature and function of single amino acids is not yet explored. Herein, we investigated the self-assembly mechanism of amyloid-like structure formation by two aromatic amino acids, phenylalanine (Phe) and tryptophan (Trp), both previously found as extremely important for the nucleation and self-assembly of aggregation-prone peptide regions into functional structures. Employing d-enantiomers, we demonstrate the critical role that amino acid chirality plays in their self-assembly process. The kinetics and morphology of pure enantiomers is completely altered upon their coassembly, allowing to fabricate different nanostructures that are mechanically more robust. Using diverse experimental techniques, we reveal the different molecular arrangement and self-assembly mechanism of the dl-racemic mixtures that resulted in the formation of advanced supramolecular materials. This study provides a simple yet sophisticated engineering model for the fabrication of attractive materials with bionanotechnological applications.
3,4-Dihydroxyphenylalanine (DOPA) is the noncanonical amino acid widely found in mussel holdfast proteins, which is proposed to be responsible for their strong wet adhesion. This feature has also inspired the successful development of a range of DOPA-containing synthetic polymers for wet adhesions and surface coating. Despite the increasing applications of DOPA in material science, the underlying mechanism of DOPA-wet surface interactions remains unclear. In this work, we studied DOPA-surface interactions one bond at a time using atomic force microscope (AFM) based single molecule force spectroscopy. With our recently developed "multiple fishhook" protocol, we were able to perform high-throughput quantification of the binding strength of DOPA to various types of surfaces for the first time. We found that the dissociation forces between DOPA and nine different types of organic and inorganic surfaces are all in the range of 60-90 pN at a pulling speed of 1000 nm s(-1), suggesting the strong and versatile binding capability of DOPA to different types of surfaces. Moreover, by constructing the free energy landscape for the rupture events, we revealed several distinct binding modes between DOPA and different surfaces, which are directly related to the chemistry nature of the surfaces. These results explain the molecular origin of the versatile binding ability of DOPA. Moreover, we could quantitatively predict the relationship between DOPA contents and the binding strength based on the measured rupture kinetics. These serve as the bases for the quantitative prediction of the relationship between DOPA contents and adhesion strength to different wet surfaces, which is important for the design of novel DOPA based materials.
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