Effect of the Activation Force of Mechanophore on Its Activation Selectivity and Efficiency in Polymer Networks.

In recent decades, more than 100 different mechanophores with a broad range of activation forces have been developed. For various applications of mechanophores in polymer materials, it is crucial to selectively activate the mechanophores with high efficiency, avoiding nonspecific bond scission of the material. In this study, we embedded cyclobutane-based mechanophore cross-linkers (I and II) with varied activation forces (fa) in the first network of the double network hydrogels and quantitively investigated the activation selectivity and efficiency of these mechanophores. Our findings revealed that cross-linker I, with a lower activation force relative to the bonds in the polymer main chain (fa-I/fa-chain = 0.8 nN/3.4 nN), achieved efficient activation with 100% selectivity. Conversely, an increase of the activation force of mechanophore II (fa-II/fa-chain = 2.5 nN/3.4 nN) led to a significant decrease of its activation efficiency, accompanied by a substantial number of nonspecific bond scission events. Furthermore, with the coexistence of two cross-linkers, significantly different activation forces resulted in the almost complete suppression of the higher-force one (i.e., I and III, fa-I/fa-III = 0.8 nN/3.4 nN), while similar activation forces led to simultaneous activations with moderate efficiencies (i.e., I and IV, fa-I/fa-IV = 0.8 nN/1.6 nN). These findings provide insights into the prevention of nonspecific bond rupture during mechanophore activation and enhance our understanding of the damage mechanism within polymer networks when using mechanophores as detectors. Besides, it establishes a principle for combining different mechanophores to design multiple mechanoresponsive functional materials.

Effect of Predamage on the Fracture Energy of Double-Network Hydrogels.

Double-network (DN) hydrogels are tough soft materials, and the high fracture resistance can be attributed to the formation of a large damage zone (internal fracture of the brittle first network) around the crack tip. In this work, we studied the effect of predamage in the brittle network on the fracture energy Γc of DN hydrogels. The prestretch of the first network was induced by prestretching the DN gels to prestretch ratio λpre. Depending on the λpre in relative to the yielding stretch ratio λy, above which the brittle first network starts to break into discontinuous fragments inside DN gels, two regimes were observed: Γc decreases monotonically with λpre in the regime of λpre < λy, mainly due to the decreasing contribution from the bulk internal damage, while Γc increases with λpre in the regime of λpre > λy. The latter can be understood by the release of the hidden length of the stretchable network strands by the rupture of the brittle network, whereby the broken fragments of the brittle network could serve as sliding cross-links to further delocalize the stress-concentration near the crack tip and prevent chain scissions.

Azobenzene as a photoswitchable mechanophore.

Azobenzene has been widely explored as a photoresponsive element in materials science. Although some studies have investigated the force-induced isomerization of azobenzene, the effect of force on the rupture of azobenzene has not been explored. Here we show that the light-induced structural change of azobenzene can also alter its rupture forces, making it an ideal light-responsive mechanophore. Using single-molecule force spectroscopy and ultrasonication, we found that cis and trans para-azobenzene isomers possess contrasting mechanical properties. Dynamic force spectroscopy experiments and quantum-chemical calculations in which azobenzene regioisomers were pulled from different directions revealed that the distinct rupture forces of the two isomers are due to the pulling direction rather than the energetic difference between the two isomers. These mechanical features of azobenzene can be used to rationally control the macroscopic fracture behaviours of polymer networks by photoillumination. The use of light-induced conformational changes to alter the mechanical response of mechanophores provides an attractive way to engineer polymer networks of light-regulatable mechanical properties.

Role of hierarchy structure on the mechanical adaptation of self-healing hydrogels under cyclic stretching.

Soft materials with mechanical adaptability have substantial potential for various applications in tissue engineering. Gaining a deep understanding of the structural evolution and adaptation dynamics of soft materials subjected to cyclic stretching gives insight into developing mechanically adaptive materials. Here, we investigate the effect of hierarchy structure on the mechanical adaptation of self-healing hydrogels under cyclic stretching training. A polyampholyte hydrogel, composed of hierarchical structures including ionic bonds, transient and permanent polymer networks, and bicontinuous hard/soft-phase networks, is adopted as a model. Conditions for effective training, mild overtraining, and fatal overtraining are demonstrated in soft materials. We further reveal that mesoscale hard/soft-phase networks dominate the long-term memory effect of training and play a crucial role in the asymmetric dynamics of compliance changes and the symmetric dynamics of hydrogel shape evolution. Our findings provide insights into the design of hierarchical structures for adaptive soft materials.

Thermoresponsive Lamellar Hydrogels with Tunable Turbidity, Structural Color, and Anisotropic Swelling.

We report a thermoresponsive anisotropic photonic hydrogel: poly(dodecyl glyceryl itaconate)/polyacrylamide-poly(N-isopropylacrylamide) hydrogel (PDGI/PAAm-PNIPAM hydrogel). Hydrogels with uniaxially aligned lamellar bilayers possess bright structural color and swelling anisotropy, while PNIPAM-based hydrogels exhibit distinct thermoresponsive properties around a lower critical solution temperature (LCST). Hybridization of thermoresponsive PNIPAM with the lamellar hydrogel can give the anisotropic photonic hydrogel various fascinating thermoresponsive properties, such as structural color/turbid transition, thermoresponsive structural color, and anisotropic deswelling/reswelling behavior by temperature stimuli. The temperature-induced changes in turbidity, structural color, and anisotropic swelling of the gel around the LCST can be tuned by controlling the incorporated PNIPAM density. PNIPAM can be regioselectively incorporated into the specific region of the lamellar hydrogels by photomasking during UV polymerization. The PDGI/PAAm-PNIPAM hydrogel can find diverse promising applications such as smart windows and smart displays.

Sustainable mechanochemical growth of double-network hydrogels supported by vascular-like perfusion.

Double-network (DN) gels are unique mechanochemical materials owing to their structures that can be dynamically remodelled during use. The mechanical energy applied to DN gels is efficiently transferred to the chemical bonds of the brittle network, generating mechanoradicals that initiate the polymerisation of pre-loaded monomers, thereby remodelling the materials. To attain continuous remodelling or growth in response to repetitive mechanical stimuli, a sustainable supply of chemical reagents to such dynamic materials is essential. In this study, inspired by the vascular perfusion transporting nutrients to cells, we constructed a circulatory system for a continuous supply of chemicals to channel-containing DN hydrogels (c-DN gels). The perfusion of monomer solutions through the channel and permeability of the c-DN gels not only replenishes the monomers consumed by the polymerisation but also replenishes the water loss caused by the surface evaporation of hydrogel, thereby freeing the mechanochemical process of DN gels from the constraints of the underwater environment. The facile chemical supply enabled us to modulate the mechanical enhancement of the c-DN gel and attain muscle-like strengthening under repeated mechanical training in deoxygenated air. We also studied the kinetics of polymer growth and strengthening and deciphered unique features of mechanochemical reaction in DN gels including the extremely long-living radicals and delayed mechanical strengthening.

Inverse mechanical-swelling coupling of a highly deformed double-network gel.

Mechanical behaviors of a polymer gel are coupled with its swelling behavior. It has been known that typical hydrogels display extension-induced swelling and drying-induced stiffening, called normal mechanical-swelling coupling. In this study, we experimentally found that highly extended double-network (DN) hydrogels exhibit abnormal inverse mechanical-swelling coupling such as extension-induced deswelling and drying-induced softening. We established theoretical hyperelastic and swelling models that reproduced all the complicated mechanical and swelling trends of the highly deformed DN hydrogels. From these theoretical analyses, it is considered that the inverse mechanical-swelling coupling of a DN gel is derived from the extreme nonlinear elasticity of its first network at its ultimate deformation state. These findings contribute toward the understanding of the mechanics of rubber-like materials up to their ultimate deformation and fracture limit.

Mechanical Model for Super-Anisotropic Swelling of the Multi-Cylindrical PDGI/PAAm Gels.

MC-PDGI/PAAm gels are cylindrical composite gels containing poly(dodecyl glyceryl itaconate) (PDGI) as a polymerized lipid oriented in a multilayer tubular shape within a polyacrylamide (PAAm) network. The most unique feature of the MC-PDGI/PAAm gel is its super-anisotropic swelling, wherein the diameter of the gel increases, but the length decreases with an increase in the volume of the gel. Through swelling and small-angle X-ray diffraction experiments, we investigated the effects of PDGI lipid bilayers and polymer network on the swelling of the MC-PDGI/PAAm gel, which suggests that the swelling anisotropy of the MC-PDGI/PAAm gel is dominated by the elasticity of the PDGI bilayers. Furthermore, we investigated the equation of state of the gel that roughly reproduced the experimental swelling results. These findings are crucial for realizing the controlled super-anisotropic swelling of MC-PDGI/PAAm gels and their applications as anisotropic actuation devices.

In Situ and Real-Time Visualization of Mechanochemical Damage in Double-Network Hydrogels by Prefluorescent Probe via Oxygen-Relayed Radical Trapping.

Visualization of mechanochemical damages, especially for those in the molecular-scale (e.g., bond scission in polymeric materials), is of great industrial and academic significance. Herein, we report a novel strategy for in situ and real-time visualization of mechanochemical damages in hydrogels by utilizing prefluorescent probes via oxygen-relayed free-radical trapping. Double-network (DN) hydrogels that generate numerous mechanoradicals by homolytic bond scission of the brittle first network at large deformation are used as model materials. Theoretical calculation suggests that mechanoradicals generated by the damage of the first network undergo an oxygen-relayed radical-transfer process which can be detected by the prefluorescent probe through the radical-radical coupling reaction. Such an oxygen-relayed radical-trapping process of the prefluorescent probe exhibits a dramatically enhanced emission, which enables the real-time sensing and visualization of mechanochemical damages in DN hydrogels made from brittle networks of varied chemical structures. To the best of authors' knowledge, this work is the first report utilizing oxygen as a radical-relaying molecule for visualizing mechanoradical damages in polymer materials. Moreover, this new method based on the probe post-loading is simple and does not introduce any chemical structural changes in the materials, outperforming most previous methods that require chemical incorporation of mechanophores into polymer networks.

Nanoscale TEM Imaging of Hydrogel Network Architecture.

In this work, the authors succeed in direct visualization of the network structure of synthetic hydrogels with transmission electron microscopy (TEM) by developing a novel staining and network fixation method. Such a direct visualization is not carried out because sample preparation and obtaining sufficient contrast are challenging for these soft materials. TEM images reveal robust heterogeneous network architectures at mesh size scale and defects at micro-scale. TEM images also reveal the presence of abundant dangling chains on the surface of the hydrogel network. The real space structural information provides a comprehensive perspective that links bulk properties with a nanoscale network structure, including fracture, adhesion, sliding friction, and lubrication. The presented method has the potential to advance the field.

Force-triggered rapid microstructure growth on hydrogel surface for on-demand functions.

Living organisms share the ability to grow various microstructures on their surface to achieve functions. Here we present a force stamp method to grow microstructures on the surface of hydrogels based on a force-triggered polymerisation mechanism of double-network hydrogels. This method allows fast spatial modulation of the morphology and chemistry of the hydrogel surface within seconds for on-demand functions. We demonstrate the oriented growth of cells and directional transportation of water droplets on the engineered hydrogel surfaces. This force-triggered method to chemically engineer the hydrogel surfaces provides a new tool in addition to the conventional methods using light or heat, and will promote the wide application of hydrogels in various fields.

Surfactant induced bilayer-micelle transition for emergence of functions in anisotropic hydrogel.

Tuning the self-assembled structures in amorphous hydrogels will enrich the functionality of hydrogels. In this study, we tuned the structure of a photonic hydrogel, which consists of polymeric lamellar bilayers entrapped inside a polyacrylamide network, simply by molecular triggering using an ionic surfactant. Owing to the binding of ionic surfactants (sodium dodecyl sulfate), the lamellar bilayers comprising non-ionic polymeric surfactants [poly(dodecyl glyceryl itaconate)] changed to micelles, whereas the unidirectional lamellar structure was preserved in the hydrogel. The bilayer-micelle structure transition caused a dramatic decrease in the swelling anisotropy and mechanical softening of the photonic gel. With the micelle structure, the softened gel shows fast (0.3 s) and reversible color change over the entire visible light range in response to a small mechanical pressure (5 kPa). This low stress-induced color-changing hydrogel could be applied as a visual tactile sensor in various fields, especially in biomedical engineering.

Azo-Crosslinked Double-Network Hydrogels Enabling Highly Efficient Mechanoradical Generation.

Double-network (DN) hydrogels have recently been demonstrated to generate numerous radicals by the homolytic bond scission of the brittle first network under the influence of an external force. The mechanoradicals thus generated can be utilized to trigger polymerization inside the gels, resulting in significant mechanical and functional improvements to the material. Although the concentration of mechanoradicals in DN gels is much higher than that in single-network hydrogels, a further increase in the mechanoradical concentration in DN gels will widen their application. In the present work, we incorporate an azoalkane crosslinker into the first network of DN gels. Compared with the traditional crosslinker N,N'-methylenebis(acrylamide), the azoalkane crosslinker causes a decrease in the yield stress but significantly increases the mechanoradical concentration of DN gels after stretching. In the azoalkane-crosslinked DN gels, the concentration of mechanoradicals can reach a maximum of ∼220 µM, which is 5 times that of the traditional crosslinker. In addition, DN gels with the azoalkane crosslinker show a much higher energy efficiency for mechanoradical generation. Interestingly, DN gels crosslinked by a mixture of azoalkane crosslinker and traditional crosslinker also exhibit excellent radical generation performance. The increase in the mechanoradical concentration accelerates polymerization and can broaden the application range of force-responsive DN gels to biomedical devices and soft robots.

Corrigendum: A Glycosylphosphatidylinositol-Anchored α-Amylase Encoded by amyD Contributes to a Decrease in the Molecular Mass of Cell Wall α-1,3-Glucan in Aspergillus nidulans.

[This corrects the article DOI: 10.3389/ffunb.2021.821946.].

How chain dynamics affects crack initiation in double-network gels.

Double-network gels are a class of tough soft materials comprising two elastic networks with contrasting structures. The formation of a large internal damage zone ahead of the crack tip by the rupturing of the brittle network accounts for the large crack resistance of the materials. Understanding what determines the damage zone is the central question of the fracture mechanics of double-network gels. In this work, we found that at the onset of crack propagation, the size of necking zone, in which the brittle network breaks into fragments and the stretchable network is highly stretched, distinctly decreases with the increase of the solvent viscosity, resulting in a reduction in the fracture toughness of the material. This is in sharp contrast to the tensile behavior of the material that does not change with the solvent viscosity. This result suggests that the dynamics of stretchable network strands, triggered by the rupture of the brittle network, plays a role. To account for this solvent viscosity effect on the crack initiation, a delayed blunting mechanism regarding the polymer dynamics effect is proposed. The discovery on the role of the polymer dynamic adds an important missing piece to the fracture mechanism of this unique material.

Experimental Verification of the Balance between Elastic Pressure and Ionic Osmotic Pressure of Highly Swollen Charged Gels.

The equilibrium swelling degree of a highly swollen charged gel has been thought to be determined by the balance between its elastic pressure and ionic osmotic pressure. However, the full experimental verification of this balance has not previously been conducted. In this study, we verified the balance between the elastic pressure and ionic osmotic pressure of charged gels using purely experimental methods. We used tetra-PEG gels created using the molecular stent method (St-tetra-PEG gels) as the highly swollen charged gels to precisely and separately control their network structure and charge density. The elastic pressure of the gels was measured through the indentation test, whereas the ionic osmotic pressure was determined by electric potential measurement without any strong assumptions or fittings. We confirmed that the two experimentally determined pressures of the St-tetra-PEG gels were well balanced at their swelling equilibrium, suggesting the validity of the aforementioned relationship. Furthermore, from single-strand level analysis, we investigated the structural requirements of the highly swollen charged gels in which the elasticity and ionic osmosis are balanced at their swelling equilibrium.

Molecular mechanism of abnormally large nonsoftening deformation in a tough hydrogel.

Tough soft materials usually show strain softening and inelastic deformation. Here, we study the molecular mechanism of abnormally large nonsoftening, quasi-linear but inelastic deformation in tough hydrogels made of hyperconnective physical network and linear polymers as molecular glues to the network. The interplay of hyperconnectivity of network and effective load transfer by molecular glues prevents stress concentration, which is revealed by an affine deformation of the network to the bulk deformation up to sample failure. The suppression of local stress concentration and strain amplification plays a key role in avoiding necking or strain softening and endows the gels with a unique large nonsoftening, quasi-linear but inelastic deformation.

Downregulation of the ypdA Gene Encoding an Intermediate of His-Asp Phosphorelay Signaling in Aspergillus nidulans Induces the Same Cellular Effects as the Phenylpyrrole Fungicide Fludioxonil.

Many eukaryotic histidine-to-aspartate (His-Asp) phosphorelay systems consist of three types of signal transducers: a His-kinase (HK), a response regulator (RR), and a histidine-containing phosphotransfer intermediate (HPt). In general, the HPt acts as an intermediate between the HK and the RR and is indispensable for inducing appropriate responses to environmental stresses. In a previous study, we attempted but were unable to obtain deletion mutants of the ypdA gene in order to characterize its function in the filamentous fungus Aspergillus nidulans. In the present study, we constructed the CypdA strain in which ypdA expression is conditionally regulated by the A. nidulans alcA promoter. We constructed CypdA strains with RR gene disruptions (CypdA-sskAΔ, CypdA-srrAΔ, and CypdA-sskAΔsrrAΔ). Suppression of YpdA induced by ypdA downregulation activated the downstream HogA mitogen-activated protein kinase cascade. YpdA suppression caused severe growth defects and abnormal hyphae, with features such as enhanced septation, a decrease in number of nuclei, nuclear fragmentation, and hypertrophy of vacuoles, both regulated in an SskA-dependent manner. Fludioxonil treatment caused the same cellular responses as ypdA suppression. The growth-inhibitory effects of fludioxonil and the lethality caused by ypdA downregulation may be caused by the same or similar mechanisms and to be dependent on both the SskA and SrrA pathways.

A Glycosylphosphatidylinositol-Anchored α-Amylase Encoded by amyD Contributes to a Decrease in the Molecular Mass of Cell Wall α-1,3-Glucan in Aspergillus nidulans.

α-1,3-Glucan is one of the main polysaccharides in the cell wall of Aspergillus nidulans. We previously revealed that it plays a role in hyphal aggregation in liquid culture, and that its molecular mass (MM) in an agsA-overexpressing (agsAOE) strain was larger than that in an agsB-overexpressing (agsBOE) strain. The mechanism that regulates its MM is poorly understood. Although the gene amyD, which encodes glycosylphosphatidylinositol (GPI)-anchored α-amylase (AmyD), is involved in the biosynthesis of α-1,3-glucan in A. nidulans, how it regulates this biosynthesis remains unclear. Here we constructed strains with disrupted amyD (ΔamyD) or overexpressed amyD (amyDOE) in the genetic background of the ABPU1 (wild-type), agsAOE, or agsBOE strain, and characterized the chemical structure of α-1,3-glucans in the cell wall of each strain, focusing on their MM. The MM of α-1,3-glucan from the agsBOE amyDOE strain was smaller than that in the parental agsBOE strain. In addition, the MM of α-1,3-glucan from the agsAOE ΔamyD strain was greater than that in the agsAOE strain. These results suggest that AmyD is involved in decreasing the MM of α-1,3-glucan. We also found that the C-terminal GPI-anchoring region is important for these functions.

Polyzwitterions as a Versatile Building Block of Tough Hydrogels: From Polyelectrolyte Complex Gels to Double-Network Gels.

The high water content of hydrogels makes them important as synthetic biomaterials, and tuning the mechanical properties of hydrogels to match those of natural tissues without changing chemistry is usually difficult. In this study, we have developed a series of hydrogels with varied stiffness, strength, and toughness based on a combination of poly(2-acrylamido-2-methylpropane sulfonic acid) (PAMPS), a strong acidic polyelectrolyte, and poly-N-(carboxymethyl)-N,N-dimethyl-2-(methacryloyloxy) ethanaminium) (PCDME), a polyzwitterion with a weak acidic moiety. We demonstrate that modifying the true molar ratio, R, of PCDME to PAMPS results in four unique categories of hydrogels with different swelling ratios and Young's moduli. When R < 1, a negatively charged polyelectrolyte gel (PE) is formed; when 1 < R < 3, a tough and viscoelastic polyelectrolyte complex gel (PEC) is formed; when 3 < R < 6.5, a conventional, elastic interpenetrating network gel (IPN) is formed; and when R > 6.5, a tough and stiff double-network gel (DN) is formed. Both the PEC and DN gels exhibit high toughness and fracture stress, up to 1.8 and 1.5 MPa, respectively. Importantly, the PEC gels exhibit strong recovery properties along with high toughness, distinguishing them from DN gels. Without requiring a change in chemistry, we can tune the mechanical response of hydrogels over a wide spectrum, making this a useful system of soft and hydrated biomaterials.