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In recent years, computational methods have become an essential element of studies focusing on the self-assembly process. Although they provide unique insights, they face challenges, from which two are the most often mentioned in the literature: the temporal and spatial scale of the self-assembly. A less often mentioned issue, but not less important, is the choice of the force-field. The repetitive nature of the supramolecular structure results in many similar interactions. Consequently, even a small deviation in these interactions can lead to significant energy differences in the whole structure. However, studies comparing different force-fields for self-assembling systems are scarce. In this article, we compare molecular dynamics simulations for trifold hydrogen-bonded fibers performed with different force-fields, namely GROMOS, CHARMM General Force Field (CGenFF), CHARMM Drude, General Amber Force-Field (GAFF), Martini, and polarized Martini. Briefly, we tested the force-fields by simulating: (i) spontaneous self-assembly (none form a fiber within 500 ns), (ii) stability of the fiber (observed for CHARMM Drude, GAFF, MartiniP), (iii) dimerization (observed for GROMOS, GAFF, and MartiniP), and (iv) oligomerization (observed for CHARMM Drude and MartiniP). This system shows that knowledge of the force-field behavior regarding interactions in oligomer and larger self-assembled structures is crucial for designing efficient simulation protocols for self-assembling systems.

Dynamic regulation of chemical reactivity is important in many complex chemical reaction networks, such as cascade reactions and signal transduction processes. Signal responsive catalysts could play a crucial role in regulating these reaction pathways. Recently, supramolecular encapsulation was reported to regulate the activities of artificial catalysts. We present a host‐guest chemistry strategy to modulate the activity of commercially available synthetic organocatalysts. The molecular container cucurbit[7]uril was successfully applied to change the activity of four different organocatalysts and one initiator, enabling up‐ or down‐regulation of the reaction rates of four different classes of chemical reactions. In most cases CB[7] encapsulation results in catalyst inhibition, however in one case catalyst activation by binding to CB[7] was observed. The mechanism behind this unexpected behavior was explored by NMR binding studies and pKa measurements. The catalytic activity can be instantaneously switched during operation, by addition of either supramolecular host or competitive binding molecules, and the reaction rate can be predicted with a kinetic model. Overall, this signal responsive system proves a promising tool to control catalytic activity., Binding an organocatalyst inside a cucurbituril molecular host can reversibly up‐ or downregulate catalytic activity, which is demonstrated in temporal control over the rate of a range of organocatalyzed transformations.

Reported here is a 2D, interfacial microcompartmentalization strategy governed by 3D phase separation. In aqueous polyethylene glycol (PEG) solutions doped with biotinylated polymers, the polymers spontaneously accumulate in the interfacial layer between the oil‐surfactant‐water interface and the adjacent polymer phase. In aqueous two‐phase systems, these polymers first accumulated in the interfacial layer separating two polymer solutions and then selectively migrated to the oil‐PEG interfacial layer. By using polymers with varying photopolymerizable groups and crosslinking rates, kinetic control and capture of spatial organisation in a variety of compartmentalized macroscopic structures, without the need of creating barrier layers, was achieved. This selective interfacial accumulation provides an extension of 3D phase separation towards synthetic compartmentalization, and is also relevant for understanding intracellular organisation., The phenomenon selective interfacial accumulation (SIA) is reported for an aqueous system. Based on interfacial migration, kinetic control and capture of the spatial organisation in a variety of compartmentalized macroscopic structures, without the need to create barrier layers between compartments, is possible. SIA opens an avenue for 3D phase separation approaches towards synthetic compartmentalized systems, and it is also relevant to understanding and mimicking intracellular organisation.

In cancer therapy, the selective targeting of cancer cells while avoiding side effects to normal cells is still full of challenges. Here, we developed dual-functionalized crescent microgels, which selectively captured and killed lung cancer cells in situ without killing other cells. Crescent microgels with the inner surface of the cavity functionalized with antibody and containing glucose oxidase (GOX) in the gel matrix have been produced in a microfluidic device. These microgels presented high affinity and good selectivity to lung cancer cells and retained them inside the cavities for extended periods of time. Exposing the crescent hydrogels to physiological concentrations of glucose leads to the production of a locally high concentration of H2O2 inside the microgels’ cavities, due to the catalytic action by GOX inside the gel matrix, which selectively killed 90 % cancer cells entrapped in the microgel cavities without killing the cells outside. Our strategy to create synergy between different functions by incorporating them in a single microgel presents a novel approach to therapeutic systems, with potentially broad applications in smart materials, bioengineering and biomedical fields.

The present work shows how transient supramolecular hydrogels can be formed by catalytically controlled molecular self-assembly. Catalysis formation of molecular gelators leads the self-assembly along a kinetically favored pathway, resulting in transient hydrogels. This work demonstrates an effective approach towards pathway-dependent supramolecular materials.

Here we report on how metastable supramolecular gels can be formed through seeded self-assembly of multicomponent gelators. Hydrazone-based gelators decorated with non-ionic and anionic groups are formed in situ from hydrazide and aldehyde building blocks, and lead through multiple self-sorting processes to the formation of heterogeneous gels approaching thermodynamic equilibrium. Interestingly, the addition of seeds composing of oligomers of gelators bypasses the self-sorting processes and accelerates the self-assembly along a kinetically favored pathway, resulting in homogeneous gels of which the network morphologies and gel stiffness are markedly different from the thermodynamically more stable gel products. Importantly, over time, these metastable homogeneous gel networks are capable of converting into the thermodynamically more stable state. This seeding-driven formation of out-of-equilibrium supramolecular structures is expected to serve as a simple approach towards functional materials with pathway-dependent properties.

Neointima (NI) healing after implantation of drug-eluting coronary stents (DES) is often preclinically evaluated in healthy swine coronary models, which only allow limited conclusions. In this study, DES were implanted in an adult familial hypercholesterolemia (FH) swine model in order to better reproduce the range of NI responses that are seen in humans. Serial OCT imaging was performed before and after stenting, and at 28 days FU. The NI response showed a wide spectrum of strut coverage types. Higher percentages baseline plaque burden resulted in more uncovered struts and heterogeneous patterns of strut coverage, uniquely showing similarities to human responses.

Atherosclerotic arteries are commonly treated using drug-eluting stents (DES). However, it remains unclear whether and how the properties of atherosclerotic plaque affect drug transport in the arterial wall. A limitation of the currently used atherosclerotic animal models to study arterial drug distribution is the unpredictability of plaque size, composition, and location. In the present study, the aim is to create an artificial atherosclerotic plaque—of reproducible and controllable complexity and implantable at specific locations—to enable systematic studies on transport phenomena of drugs in stented atherosclerosis-mimicking arteries. For this purpose, mixtures of relevant lipids at concentrations mimicking atherosclerotic plaque are incorporated in gelatin/alginate hydrogels. Lipid-free (control) and lipid-rich hydrogels (artificial plaque) are created, mounted on DES and successfully implanted in porcine coronary arteries ex-vivo. Matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI) is used to measure local drug distribution in the arterial wall behind the prepared hydrogels, showing that the lipid-rich hydrogel significantly hampers drug transport as compared to the lipid-free hydrogel. This observation confirms the importance of studying drug transport phenomena in the presence of lipids and of having an experimental model in which lipids and other plaque constituents can be precisely controlled and systematically studied.

Properties such as shear modulus, gelation time, structure of supramolecular hydrogels are strongly dependent on self‐assembly, gelation triggering mechanism and processes used to form the gel. In our work we extend reported rheology analysis methodologies to pH‐triggered supramolecular gels to understand structural insight using a model system based on N−N’ Dibenzoyl‐L‐Cystine pH‐triggered hydrogelator and Glucono‐δ‐Lactone as the trigger. We observed that Avrami growth model when applied to time‐sweep rheological data of gels formed at lower trigger concentrations provide estimates of fractal dimension which agree well compared with visualization of the microstructure as seen via Confocal Laser Scanning Microscopy, for a range of gelator concentrations., Unlocking microstructure via the mechanical properties of hydrogels: Using rheology, mathematical models and confocal laser scanning microscopy, the gelation of a pH‐triggered low molecular weight gelator is studied using an acid trigger. For a range of gelator and trigger concentrations, Avrami model predictions agree with confocal micrographs. The work helps extend models created on temperature‐triggered gelators to chemically‐triggered systems.

The adhesiveness of biological micropatterned adhesives primarily relies on their geometry (e.g., feature size, architecture) and material properties (e.g., stiffness). Over the last few decades, researchers have been mimicking the geometry and material properties of biological micropatterned adhesives. The performance of these biomimetic micropatterned adhesives is usually tested on hard substrates. Much less is known about the effect of geometry, feature size, and material properties on the performance of micropatterned adhesives when the substrate is deformable. Here, micropatterned adhesives of two stiffness degrees (Young’s moduli of 280 and 580 kPa) were fabricated from poly(dimethylsiloxane) (PDMS) and tested on soft poly(vinyl alcohol) (PVA) substrates of two stiffness degrees (12 and 18 kPa), and on hard glass substrates as a reference. An out-of-the-cleanroom colloidal lithographic approach was successfully expanded to fabricate adhesives with two geometries, namely dimples with and without a terminal layer. Dimples without a terminal layer were fabricated on two length scales, namely with sub-microscale and microscale dimple diameters. The cross section of samples with a terminal layer showed voids with a spherical shape, separated by hourglass-shaped walls. These voids penetrate the terminal layer, resulting in an array of holes at the surface. We found that on soft substrates, generally, the size of the dimples did not affect pull-off forces. The positive effects of sub-microscale features on pull-off and friction forces, such as defect control and crack trapping, as reported in the literature for hard substrates, seem to disappear on soft substrates. The dimple geometry with a terminal layer generated significantly higher pull-off forces compared to other geometries, presumably due to interlocking of the soft substrate into the holes of the terminal layer. Pull-off from soft substrates increased with the substrate stiffness for all tested geometries. Friction forces on soft substrates were the highest for microscale dimples without a terminal layer, likely due to interlocking of the soft substrate between the dimples.

Gelled lyotropic liquid crystals (LLCs) are highly tunable multi-component materials. By studying a selection of low molecular weight gelators (LMWGs), we find gelators that form self-assembled gels in LLCs without influencing their phase boundaries. We studied the system H2O/NaCl-Genapol LA070 in the presence of (a) the organogelators 12-hydroxyoctadecanoic acid (12-HOA) and 1,3:2,4-dibenzylidene-d-sorbitol (DBS) and (b) the hydrogelators N,N'-dibenzoyl-l-cystine (DBC) and a tris-amido-cyclohexane derivative (HG1). Visual phase studies and oscillation shear frequency sweeps confirmed that 12-HOA acts as co-surfactant (stabilizing the lamellar Lα phase and destabilizing the hexagonal H1 phase), thus preventing gelation. Conversely, DBS was a potent gelator for LLCs, with the phase boundaries un-influenced by the presence of DBS; gelled lamellar Lα, and softly-gelled hexagonal H1 phases are formed. For the hydrogelator DBC, the LLC phase boundaries were only slightly altered, but no gelled LLCs were formed. For the hydrogelator HG1, however, the phase boundaries were unaffected while gelled lamellar Lα and softly-gelled hexagonal H1 phases were formed. Temperature-dependent rheology measurements demonstrated that by changing the DBS or the HG1 concentration, the sol-gel transition temperature of the gelled lamellar Lα phase can be adjusted such that (a) Tsol-gel is below the Lα-isotropic phase transition (DBS, HG1 mass fraction η = 0.0075) and (b) Tsol-gel is above the gelled Lα-isotropic phase transition (DBS, HG1 η = 0.015). This opens the possibility of temporal materials control by addressing phase transitions in different orders. As this system contains oil and water, both the organogelator DBS and the hydrogelator HG1 can gel these LLCs, but this clearly does not apply to all organogelators/hydrogelators. The study indicates that careful optimization of LMWGs is required to avoid interaction with the surfactant layer and to optimize the Tsol-gel value, which is important for the application of LMWGs in gelled LLCs.

Here, transient supramolecular hydrogels that are formed through simple aging‐induced seeded self‐assembly of molecular gelators are reported. In the involved molecular self‐assembly system, multicomponent gelators are formed from a mixture of precursor molecules and, typically, can spontaneously self‐assemble into thermodynamically more stable hydrogels through a multilevel self‐sorting process. In the present work, it is surprisingly found that one of the precursor molecules is capable of self‐assembling into nano‐sized aggregates upon a gentle aging treatment. Importantly, these tiny aggregates can serve as seeds to force the self‐assembly of gelators along a kinetically controlled pathway, leading to transient hydrogels that eventually spontaneously convert into thermodynamically more stable hydrogels over time. Such an aging‐induced seeded self‐assembly process is not only a new route toward synthetic out‐of‐equilibrium supramolecular systems, but also suggests the necessity of reporting the age of self‐assembling building block solutions in other self‐assembly systems., A simple aging‐induced seeded self‐assembly resulting in transient supramolecular hydrogels is reported. The obtained transient hydrogels can convert into the thermodynamically more stable state over time. The findings demonstrate a new route toward out‐of‐equilibrium self‐assembly system, and suggest the necessity of stating the ages of self‐assembling building blocks in some other supramolecular systems.

Hydrogel microparticles are important in materials engineering, but their applications remain limited owing to the difficulties associated with their manipulation. Herein, we report the self‐orientation of crescent‐shaped hydrogel microparticles and elucidate its mechanism. Additionally, the microparticles were used, for the first time, as micro‐buckets to carry living cells. In aqueous solution, the microparticles spontaneously rotated to a preferred orientation with the cavity facing up. We developed a geometric model that explains the self‐orienting behavior of crescent‐shaped particles by minimizing the potential energy of this specific morphology. Finally, we selectively modified the particles’ cavities with RGD peptide and exploited their preferred orientation to load them with living cells. Cells could adhere, proliferate, and be transported and released in vitro. These micro‐buckets hold a great potential for applications in smart materials, cell therapy, and biological engineering.

While the formation of (tri)block copolymer hydrogels has been extensively investigated, such studies mostly focused on equilibrium self-assembling whereas the use of preformed structures as building blocks such as out of equilibrium, quenched, nanofibrillar micelles is still a challenge. Here, we demonstrate that quenched, ultralong polystyrene-b-poly(ethylene oxide) (PS-b-PEO) micelles can be used as robust precursors of hydrogels. Two cross-linking strategies, (i) thermal fusion of micellar cores and (ii) chemical cross-linking of preformed micellar coronas were studied. The gelation process and the structure of the micellar networks were investigated by in situ rheological measurements, confocal microscopy and transmission electron microscopy. Direct observation of core fusion of preformed quenched micelles is provided validating this method as a robust gelation route. Using time sweep rheological experiments, it was found for both cross-linking methods that these 3D "mikado" gels are formed in three different stages, containing (1) initiation, (2) transition (growth), and (3) stabilization regimes.

The amino acid profile obtained from a fingerprint may provide valuable information on its donor. For forensic scientists, recovering evidence relating to the amino acid profile of a suspect can potentially be valuable for identification and exclusion purposes. Herein we detail the use of cross-linkable solutions of dextran-methacrylate to form hydrogels capable of collecting amino acids from surfaces followed by extraction and quantification with UPLC-MS. This method allows for the amino acid profile analysis of fingerprints while allowing for their increased visualisation at a later stage using the standard method of cyanoacrylation. We will demonstrate this method to also be capable of collecting DNA from fingerprints with a 20-60% yield in comparison to using a conventional cotton swab.

Self-assembly provides access to a variety of molecular materials, yet spatial control over structure formation remains difficult to achieve. Here we show how reaction–diffusion (RD) can be coupled to a molecular self-assembly process to generate macroscopic free-standing objects with control over shape, size, and functionality. In RD, two or more reactants diffuse from different positions to give rise to spatially defined structures on reaction. We demonstrate that RD can be used to locally control formation and self-assembly of hydrazone molecular gelators from their non-assembling precursors, leading to soft, free-standing hydrogel objects with sizes ranging from several hundred micrometres up to centimeters. Different chemical functionalities and gradients can easily be integrated in the hydrogel objects by using different reactants. Our methodology, together with the vast range of organic reactions and self-assembling building blocks, provides a general approach towards the programmed fabrication of soft microscale objects with controlled functionality and shape.

We report on the biocatalytic activation of a self-assembling (unprotected) tripeptide to stabilize oil-in-water emulsions on-demand. This is achieved by the conversion of a phosphorylated precursor into a hydrogelator using alkaline phosphatase (AP) as the trigger. The rate of conversion, controlled by the amount of enzyme used, is shown to play a key role in dictating the morphology of the nanofibrous networks produced. When these amphiphilic tripeptides are used in biphasic mixtures, nanofibers are shown to self-assemble not only at the aqueous/organic interface but also throughout the surrounding buffer, thereby stabilizing the oil-in-water droplet dispersions. The use of enzymatic activation of tripeptide emulsions gives rise to enhanced control of the emulsification process because emulsions can be stabilized on-demand by simply adding AP. In addition, control over the emulsion stabilization can be achieved by taking advantage of the kinetics of dephosphorylation and consequent formation of different stabilizing nanofibrous networks at the interface and/or in the aqueous environment. This approach can be attractive for various cosmetic, food, or biomedical applications because both tunability of the tripeptide emulsion stability and on-demand stabilization of emulsions can be achieved.

We report a flexible single-cell isolation method by imaging-assisted hydrogel formation. Our approach consists of imaging-aided selective capture of cells of interest by encasing them into a polymeric hydrogel, followed by removal of unwanted cells and subsequent release of isolated cells by enzymatic hydrogel degradation, thus offering an opportunity for further analysis or cultivation of selected cells. We achieved high sorting efficiency and observed excellent viability rates (>98%) for NIH/3T3 fibroblasts and A549 carcinoma cells isolated using this procedure. The method presented here offers a mask-free, cost-efficient and easy-to-use alternative to many currently existing surface-based cell-sorting techniques, and has the potential to impact the field of cell culturing and isolation, e.g. single cell genomics and proteomics, investigation of cellular heterogeneity and isolation of best performing mutants for developing new cell lines.

Supramolecular assemblies are promising building blocks for the fabrication of functional soft devices for high-tech applications. However, there is a lack of effective methods for large-scale manipulation and integration of nano-sized supramolecular structures on soft substrate. Now, functional soft devices composed of micellar filaments and hydrogels can be created through a versatile approach involving guided dewetting, transfer-printing, and laser-assisted patterning. Such an approach enables unprecedented control over the location and alignment of the micellar filaments on hydrogel substrates. As examples, freely suspended micellar fishnets immobilized on hydrogels are formed, showing the capability of trapping and releasing micro-objects and the piconewton force sensitivity. By incorporating responsive moieties into hydrogels, shape-morphing actuators with micelle-controlled rolling directionality are constructed.

Controlled localization of platinum nanoparticles (Pt NPs) at a solid support assisted by a polarized liquid-liquid interface is reported. Electrocatalytic water oxidation resulted in local pH modulation followed by the directed self-assembly of a dibenzoyl-l-cystine hydrogelator forming a structured hydrogel retaining the shape of the Pt NP deposit.

Gelled lyotropic liquid crystals (LLCs) are highly tunable multi-component materials. By studying a selection of low molecular weight gelators (LMWGs), we find gelators that form self-assembled gels in LLCs without influencing their phase boundaries. We studied the system H2O/NaCl-Genapol LA070 in the presence of (a) the organogelators 12-hydroxyoctadecanoic acid (12-HOA) and 1,3:2,4-dibenzylidene-d-sorbitol (DBS) and (b) the hydrogelators N,N'-dibenzoyl-l-cystine (DBC) and a tris-amido-cyclohexane derivative (HG1). Visual phase studies and oscillation shear frequency sweeps confirmed that 12-HOA acts as co-surfactant (stabilizing the lamellar Lα phase and destabilizing the hexagonal H1 phase), thus preventing gelation. Conversely, DBS was a potent gelator for LLCs, with the phase boundaries un-influenced by the presence of DBS; gelled lamellar Lα, and softly-gelled hexagonal H1 phases are formed. For the hydrogelator DBC, the LLC phase boundaries were only slightly altered, but no gelled LLCs were formed. For the hydrogelator HG1, however, the phase boundaries were unaffected while gelled lamellar Lα and softly-gelled hexagonal H1 phases were formed. Temperature-dependent rheology measurements demonstrated that by changing the DBS or the HG1 concentration, the sol-gel transition temperature of the gelled lamellar Lα phase can be adjusted such that (a) Tsol-gel is below the Lα-isotropic phase transition (DBS, HG1 mass fraction η = 0.0075) and (b) Tsol-gel is above the gelled Lα-isotropic phase transition (DBS, HG1 η = 0.015). This opens the possibility of temporal materials control by addressing phase transitions in different orders. As this system contains oil and water, both the organogelator DBS and the hydrogelator HG1 can gel these LLCs, but this clearly does not apply to all organogelators/hydrogelators. The study indicates that careful optimization of LMWGs is required to avoid interaction with the surfactant layer and to optimize the Tsol-gel value, which is important for the application of LMWGs in gelled LLCs.

Transient materials that function out-of-equilibrium have been of great interest due to their unique properties that are rarely observed in thermodynamically stable occasions. However, the current advances are still limited to supramolecular objects, and the applications using this transient nature remain largely unexplored. Herein we report on chemical fuel powered transient polymer hydrogels for controlled formation and free release of pharmaceutical crystals. The transient polymer hydrogels with highly tunable stiffness and lifetime were created by chemical fuel powered crosslinking, which can be well regenerated without obvious deteriorations by simply refueling. On the basis of these properties, especially the transient nature, these hydrogels can serve as novel reusable platforms to control the pharmaceutical crystallization, more importantly, freely release the obtained crystals, which is inaccessible by conventional static gels. This work is expected to serve as an example to accelerate the development of more advanced out-of-equilibrium materials and exploitations of their high-tech applications.

To examine the mechanism of the network formation of silk fibroin (SF), monodispersed colloidal particles (MDCPs) are used as well defined foreign substrates to quantify their effect on the primary nucleation of β-crystallites in molecular networks (silk nanofibrils) and the hierarchical network formation of SF. It follows that MDCPs are capable of accelerating the SF gelation by reducing the multistep nucleation barrier, which gives rise to a high density of silk fibril domain networks due to the increase of primary nucleation sites. Consequently, through governing the change in the hierarchical mesoscopic structure, the macroscopic performance of silk materials (e.g., the rheological properties of SF hydrogels and the tensile stress of fibers) can be controlled directly. As SF hydrogels represent a typical example of weak fibril domain–domain network interactions, the increase of fibril domain density leads to weaker gels. On the other hand, SF fibers correspond to strong fibril domain–domain network interactions, the increase of fibril domain density ends up with much tougher fibers. The knowledge obtained provides a facile strategy in controlling the complex hierarchical structure and macroscopic performance of SF materials, and offers useful routes for general design and functionalization of soft materials.

In this contribution we show that biological membranes can catalyze the formation of supramolecular hydrogel networks. Negatively charged lipid membranes can generate a local proton gradient, accelerating the acid-catalyzed formation of hydrazone-based supramolecular gelators near the membrane. Synthetic lipid membranes can be used to tune the physical properties of the resulting multicomponent gels as a function of lipid concentration. Moreover, the catalytic activity of lipid membranes and the formation of gel networks around these supramolecular structures are controlled by the charge and phase behavior of the lipid molecules. Finally, we show that the insights obtained from synthetic membranes can be translated to biological membranes, enabling the formation of gel fibers on living HeLa cells.

This work describes a facile approach allowing Dibenzoyl- l -Cystine (DBC) based hydrogel controlled deposition and controlled detachments over a conducting support. The method itself is an electrochemically assisted approach, where the water oxidation at the electrode surface results in a local pH drop inducing DBC gelation and hydrogel formation. We have comprehensively described the possibility of the hydrogel shaping by alternating the anodic deposition potential, DBC concentration and finally the working electrode geometry. The latter includes macro-electrodes in a form of platinum discs having diameter equal to 200 and 500 μm; hexagonal arrays of circular platinum microelectrodes with a diameter of a single electrode equal to 5 or 10 μm and custom made platinum microelectrodes, having the shape of circles, triangles and squares, that are used to shape the microgels. Over the course of our work we were able to define the conditions to form a number of different hydrogel shapes such as: (i) flat and planar deposits; (ii) hemispherical deposits with an oxygen bubble pocket; (iii) spongy hydrogel structures or (iv) hemispherical micro-cups build from radially oriented DBC fibres directionally growing from the support. Furthermore, we were also able to remotely form and then detach the hydrogel deposit in the initial formulation solution using only an electrochemical trigger. Our work represents a solid proof of concept and opens a number of new avenues for the electrochemically assisted soft matter fabrication down to micrometre scale.

Hierarchical compartmentalization through the bottom-up approach is ubiquitous in living cells but remains a formidable task in synthetic systems. Here we report on hierarchically compartmentalized supramolecular gels that are spontaneously formed by multilevel self-sorting. Two types of molecular gelators are formed in situ from nonassembling building blocks and self-assemble into distinct gel fibers through a kinetic self-sorting process; interestingly, these distinct fibers further self-sort into separated microdomains, leading to microscale compartmentalized gel networks. Such spontaneously multilevel self-sorting systems provide a "bottom-up" approach toward hierarchically structured functional materials and may play a role in intracellular organization.

Controlled diffusion, reaction and assembly of hydrogelator precursors can be used to create soft hydrogel objects of defined shape and size. In this study we show that controlling local reaction kinetics by means of pH, diffusion length and the concentrations of reactants allows control over the dimensions of formed supramolecular structures. By correlating a reaction diffusion model to experimental results, we show that the influence of all these control parameters can be unified using the Damko hler number, thus providing an easy-to-use relation between experimental parameters and structure dimensions. Finally, our study suggests that control over concentration gradients and chemical reactivity in combination with supramolecular chemistry is a promising platform for the design of soft matter objects of defined sizes, a concept that has received little attention up until now.

Herein, the micropatterning of supramolecular gels with oriented growth direction and controllable spatial dimensions by directing the self-assembly of small molecular gelators is reported. This process is associated with an acid-catalyzed formation of gelators from two soluble precursor molecules. To control the localized formation and self-assembly of gelators, micropatterned poly(acrylic acid) (PAA) brushes are employed to create a local and controllable acidic environment. The results show that the gel formation can be well confined in the catalytic surface plane with dimensions ranging from micro- to centimeter. Furthermore, the gels show a preferential growth along the normal direction of the catalytic surface, and the thickness of the resultant gel patterns can be easily controlled by tuning the grafting density of PAA brushes. This work shows an effective "bottom-up" strategy toward control over the spatial organization of materials and is expected to find promising applications in, e.g., microelectronics, tissue engineering, and biomedicine.

A novel and facile approach to fabricating well-organized macroscopic 2D networks of cylindrical micelles is reported, based on transfer printing and thermal welding of aligned supramolecular micelles of block copolymers. This versatile approach provides a new strategy for fabricating functional 2D superstructures with a higher level of order.

We report the orthogonal assembly of two structurally dissimilar catalytic hydrogelators with mutually incompatible functional groups able to retain their individual catalytic activity and thus catalyse tandem reactions in one pot., By equipping mutually incompatible carboxylic acid and proline catalytic groups with different self-assembling motives we have achieved self-sorting of the resulting catalytic gelators, namely SucVal8 and ProValDoc, into different supramolecular fibers, thus preventing the acidic and basic catalytic groups from interfering with each other. The resulting spatial separation of the incompatible catalytic functions is found to be essential to achieve one-pot deacetalization–aldol tandem reactions with up to 85% efficiency and 90% enantioselectivity. On the contrary, when SucVal8 was co-assembled with a structurally similar catalytically active hydrogelator (ProVal8), self-sorting was precluded and no tandem catalysis was observed.

Protein immobilization on surfaces, and on lipid bilayers specifically, has great potential in biomolecular and biotechnological research. Of current special interest is the immobilization of proteins using supramolecular noncovalent interactions. This allows for a reversible immobilization and obviates the use of harsh ligation conditions that could denature fragile proteins. In the work presented here, reversible supramolecular immobilization of proteins on lipid bilayer surfaces was achieved by using the host-guest interaction of the macrocyclic molecule cucurbit[8]uril. A fluorescent protein was successfully immobilized on the lipid bilayer by making use of the property of cucurbit[8]uril to host together a methylviologen and the indole of a tryptophan positioned on the N-terminal of the protein. The supramolecular complex was anchored to the bilayer through a cholesterol moiety that was attached to the methylviologen tethered with a small polyethylene glycol spacer. Protein immobilization studies using a quartz crystal microbalance (QCM) showed the assembly of the supramolecular complexes on the bilayer. Specific immobilization through the protein N-terminus is more efficient than through protein side-chain events. Reversible surface release of the proteins could be achieved by washing with cucurbit[8]uril or buffer alone. The described system shows the potential of supramolecular assembly of proteins and provides a method for site-specific protein immobilization under mild conditions in a reversible manner. ? 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Simultaneous control of the kinetics and thermodynamics of two different types of covalent chemistry allows pathway selectivity in the formation of hydrogelating molecules from a complex reaction network. This can lead to a range of hydrogel materials with vastly different properties, starting from a set of simple starting compounds and reaction conditions. Chemical reaction between a trialdehyde and the tuberculosis drug isoniazid can form one, two, or three hydrazone connectivity products, meaning kinetic gelation pathways can be addressed. Simultaneously, thermodynamics control the formation of either a keto or an enol tautomer of the products, again resulting in vastly different materials. Overall, this shows that careful navigation of a reaction landscape using both kinetic and thermodynamic selectivity can be used to control material selection from a complex reaction network.

Hydrazone formation reactions from aldehydes and hydrazides have the remarkable qualities that they proceed in water and the kinetics can be controlled by organocatalysis. For these reasons, this class of reactions finds widespread use in biological as well as material settings. We recently reported a protected aniline catalyst for hydrazone formation that can be activated using a chemical signal. In our search to find a suitable hydrazone formation reaction to investigate the activation of this pro-catalyst, we found a wide variety in reaction rates and response to catalysis. Here we report an overview of hydrazone formation reactions, their reaction rates and response to aniline catalysis, their compatibility for kinetic analysis by UV/Vis spectroscopy, and their compatibility with the reaction environment and with the pro-catalyst pro-aniline.

The work presented here shows that the growth of supramolecular hydrogel fibers can be spatially directed at the nanoscale by catalytic negatively charged nanoparticles (NCNPs). The NCNPs with surfaces grafted with negatively charged polymer chains create a local proton gradient that facilitates an acid-catalyzed formation of hydrogelators in the vicinity of NCNPs, ultimately leading to the selective formation of gel fibers around NCNPs. The presence of NCNPs has a dominant effect on the properties of the resulting gels, including gelation time, mechanical properties, and network morphology. Interestingly, local fiber formation can selectively entrap and precipitate out NCNPs from a mixture of different nanoparticles. These findings show a new possibility to use directed molecular self-assembly to selectively trap target nano-objects, which may find applications in therapy, such as virus infection prevention, or engineering applications, like water treatment and nanoparticle separation.

Cells can react to their environment by changing the activity of enzymes in response to specific chemical signals. Artificial catalysts capable of being activated by chemical signals are rare, but of interest for creating autonomously responsive materials. We present an organocatalyst that is activated by a chemical signal, enabling temporal control over reaction rates and the formation of materials. Using self-immolative chemistry, we design a deactivated aniline organocatalyst that is activated by the chemical signal hydrogen peroxide and catalyses hydrazone formation. Upon activation of the catalyst, the rate of hydrazone formation increases 10-fold almost instantly. The responsive organocatalyst enables temporal control over the formation of gels featuring hydrazone bonds. The generic design should enable the use of a large range of triggers and organocatalysts, and appears a promising method for the introduction of signal response in materials, constituting a first step towards achieving communication between artificial chemical systems., Enzymes regulated by chemical signals are common in biology, but few such artificial catalysts exist. Here, the authors design an aniline catalyst that, when activated by a chemical trigger, catalyses formation of hydrazone-based gels, demonstrating signal response in a soft material.

The use of dissipative self-assembly driven by chemical reaction networks for the creation of unique structures is gaining in popularity. In dissipative self-assembly, precursors are converted into self-assembling building blocks by the conversion of a source of energy, typically a photon or a fuel molecule. The self-assembling building block is intrinsically unstable and spontaneously reverts to its original precursor, thus giving the building block a limited lifetime. As a result, its presence is kinetically controlled, which gives the associated supramolecular material unique properties. For instance, formation and properties of these materials can be controlled over space and time by the kinetics of the coupled reaction network, they are autonomously self-healing and they are highly adaptive to small changes in their environment. By means of an example of a biological dissipative self-assembled material, the unique concepts at the basis of these supramolecular materials will be discussed. We then review recent efforts towards man-made dissipative assembly of structures and how their unique material properties have been characterized. In order to help further the field, we close with loosely defined design rules that are at the basis of the discussed examples.

Self-assembly provides access to a variety of molecular materials, yet spatial control over structure formation remains difficult to achieve. Here we show how reaction–diffusion (RD) can be coupled to a molecular self-assembly process to generate macroscopic free-standing objects with control over shape, size, and functionality. In RD, two or more reactants diffuse from different positions to give rise to spatially defined structures on reaction. We demonstrate that RD can be used to locally control formation and self-assembly of hydrazone molecular gelators from their non-assembling precursors, leading to soft, free-standing hydrogel objects with sizes ranging from several hundred micrometres up to centimeters. Different chemical functionalities and gradients can easily be integrated in the hydrogel objects by using different reactants. Our methodology, together with the vast range of organic reactions and self-assembling building blocks, provides a general approach towards the programmed fabrication of soft microscale objects with controlled functionality and shape., Reaction-diffusion controls the spatial formation of many natural structures but is rarely applied to organic materials. Here, the authors couple reaction-diffusion to the self-assembly of a supramolecular gelator, introducing a strategy to forming soft, free-standing objects with controlled shape and functionality.

A generic method is used for compartmentalization of supramolecular hydrogels by using water-in-water emulsions based on aqueous multi-phase systems (AMPS). By forming the low-molecular-weight hydrogel throughout all phases of all-aqueous emulsions, distinct, micro-compartmentalized materials were created. This structuring approach offers control over the composition of each type of the compartments by directing the partitioning of objects to be encapsulated. Moreover, this method allows for barrier-less, dynamic exchange of even large hydrophilic solutes (MW≈60 kDa) between separate aqueous compartments. These features are expected to find use in the fields of, for instance, micro-structured catalysts, templating, and tissue engineering.

Self-assembly of biomolecules catalytically controls the formation of natural supramolecular structures, giving highly ordered complex materials. Such desirable hybrid systems are very difficult to design and construct synthetically. A hybrid double-network hydrogel with a maximum storage modulus (G'max ) of up to 55 kPa can be synthesized by using a self-assembled hydrogel that catalyses the formation of another kinetically arrested hydrogel network. Tuning of the catalytic efficiency of the first network allowed spatiotemporal control over the evolution of the second network and the resulting mechanical properties. The distribution of active catalytic sites was optimal for catalytic fibres prepared at the minimum gelation concentration (MGC) to give the double-network hydrogel with highest storage modulus. This approach could be very useful in preparing complex hierarchical structures with tailor-made properties.

This protocol details the preparation of low-molecular-weight hydrogels (LMWGs) in which the gelation time and mechanical stiffness of the final gel can be tuned with the concentration of the catalyst used in the in situ formation of the hydrogelator. By altering the rate of formation of the hydrazone-based gelator from two water-soluble compounds--an oligoethylene functionalized benzaldehyde and a cyclohexane-derived trishydrazide--in the presence of acid or aniline as catalyst, the kinetics of gelation can be tuned from hours to minutes. The resulting materials display controllable stiffness in the 5-50 kPa range. This protocol works at ambient temperatures in water, at either neutral or moderately acidic pH (phosphate buffer, pH 5) depending on the catalyst used. The hydrazide and aldehyde precursors take a total of 5 d to prepare. The final gel is prepared by mixing aqueous solutions of the two precursors and can take between minutes and hours to set, depending on the catalytic conditions. We also describe analysis of the hydrogels by critical gel concentration (CGC) tests, rheology and confocal laser-scanning microscopy (CLSM).