Consequences of a cosolvent on the structure and molecular dynamics of supramolecular polymers in water

\u3cp\u3ePolar cosolvents are commonly used to guide the self-assembly of amphiphiles in water. Here we investigate the influence of the cosolvent acetonitrile (ACN) on the structure and dynamics of a supramolecular polymer in water, which is based on the well-known benzene-1,3,5-tricarboxamide motif. Hydrogen/deuterium exchange mass spectroscopy measurements show that a gradual increase in the amount of ACN results in a gradual increase in the exchange dynamics of the monomers. In contrast, the morphology of the supramolecular polymers remains unchanged up to 15% of ACN, but then an abrupt change occurs and spherical aggregates are formed. Remarkably, this abrupt change coincides with the formation of micro-heterogeneity in the water-ACN mixtures. The results illustrate that in order to completely characterize supramolecular polymers it is important to add time-resolved measurements that probe their dynamic behavior, to the conventional techniques that are used to assess the morphology of the polymers. Subsequently we have used time-resolved measurements to investigate the influence of the concentration of ACN on the polymerization and depolymerization rates of the supramolecular polymers. Polymerization occurs within minutes when molecularly dissolved monomers are injected from ACN into water and is independent of the fraction of ACN up to 15%. In the depolymerization experiments - initiated by mixing equilibrated supramolecular polymers with dissolved monomers - the equilibration of the system takes multiple hours and does depend on the fraction of ACN. Interestingly, the longest equilibration time of the polymers is observed at a critical solvent composition of around 15% ACN. The differences in the timescales detected in the polymerization and depolymerization experiments are likely correlated to the non-covalent interactions involved, namely the hydrophobic effect and hydrogen-bonding interactions. We attribute the observed fast kinetics in the polymerization reactions to the hydrophobic effect, whereas the formation of intermolecular hydrogen bonds is the retarding factor in the equilibration of the polymers in the depolymerization experiments. Molecular dynamics simulations show that the latter is a likely explanation because ACN interferes with the hydrogen bonds and loosens the internal structure of the polymers. Our results highlight the importance of the solution conditions during the non-covalent synthesis of supramolecular polymers, as well as after equilibration of the polymers.\u3c/p\u3

Controlling protein activity by dynamic recruitment on a supramolecular polymer platform

\u3cp\u3eNature uses dynamic molecular platforms for the recruitment of weakly associating proteins into higher-order assemblies to achieve spatiotemporal control of signal transduction. Nanostructures that emulate this dynamic behavior require features such as plasticity, specificity and reversibility. Here we introduce a synthetic protein recruitment platform that combines the dynamics of supramolecular polymers with the programmability offered by DNA-mediated protein recruitment. Assembly of benzene-1,3,5-tricarboxamide (BTA) derivatives functionalized with a 10-nucleotide receptor strand into μm-long supramolecular BTA polymers is remarkably robust, even with high contents of DNA-functionalized BTA monomers and associated proteins. Specific recruitment of DNA-conjugated proteins on the supramolecular polymer results in a 1000-fold increase in protein complex formation, while at the same time enabling their rapid exchange along the BTA polymer. Our results establish supramolecular BTA polymers as a generic protein recruitment platform and demonstrate how assembly of protein complexes along the supramolecular polymer allows efficient and dynamic control of protein activity. DNA-origami allows the precise recruitment of DNA-protein conjugates but lacks the dynamics found in natural protein assemblies. Here the authors present a synthetic polymer platform that combines the dynamics of supramolecular polymers with the programmability of DNA-mediated protein recruitment.\u3c/p\u3

Strain stiffening hydrogels through self-assembly and covalent fixation of semi-flexible fibers

Biomimetic, strain-stiffening materials are reported, made through self-assembly and covalent fixation of small building blocks to form fibrous hydrogels that are able to stiffen by an order of magnitude in response to applied stress. The gels consist of semi-flexible rodlike micelles of bisurea bolaamphiphiles with oligo(ethylene oxide) (EO) outer blocks and a polydiacetylene (PDA) backbone. The micelles are fibers, composed of 9–10 ribbons. A gelation method based on Cu-catalyzed azide–alkyne cycloaddition (CuAAC), was developed and shown to lead to strain-stiffening hydrogels with unusual, yet universal, linear and nonlinear stress–strain response. Upon gelation, the X-ray scattering profile is unchanged, suggesting that crosslinks are formed at random positions along the fiber contour without fiber bundling. The work expands current knowledge about the design principles and chemistries needed to achieve fully synthetic, biomimetic soft matter with on-demand, targeted mechanical properties

Monosaccharides as versatile units for water-soluble supramolecular polymers

\u3cp\u3eWe introduce monosaccharides as versatile water-soluble units to compatibilise supramolecular polymers based on the benzene-1,3,5-tricarboxamide (BTA) moiety with water. A library of monosaccharide-based BTAs is evaluated, varying the length of the alkyl chain (hexyl, octyl, decyl and dodecyl) separating the BTA and saccharide units, as well as the saccharide units (α-glucose, β-glucose, α-mannose and α-galactose). In all cases, the monosaccharides impart excellent water compatibility. The length of the alkyl chain is the determining factor to obtain either long, one-dimensional supramolecular polymers (dodecyl spacer), small aggregates (decyl spacer) or molecularly dissolved (octyl and hexyl) BTAs in water. For the BTAs comprising a dodecyl spacer, our results suggest that a cooperative self-assembly process is operative and that the introduction of different monosaccharides does not significantly change the self- assembly behaviour. Finally, we investigate the potential of post-assembly functionalisation of the formed supramolecular polymers by taking advantage of dynamic covalent bond formation between the monosaccharides and benzoxaboroles. We observe that the supramolecular polymers readily react with a fluorescent benzoxaborole derivative permitting imaging of these dynamic complexes by confocal fluorescence microscopy.\u3c/p\u3

Impact of the water-compatible periphery on the dynamic and structural properties of benzene-1,3,5-tricarboxamide based amphiphiles

\u3cp\u3eThe consequences of using saccharides versus tetra(ethyleneglycol) chains as water-compatible moieties on the morphology and dynamics of supramolecular polymers in aqueous solutions are investigated. The saccharides form many H-bonds with other saccharides within the polymer and with water, increasing the hydration of the fiber and changing its dynamics.\u3c/p\u3

Controlling and tuning the dynamic nature of supramolecular polymers in aqueous solutions

\u3cp\u3eStructural and kinetic exchange properties of supramolecular polymers composed of mono- and bivalent ureidopyrimidinone-based monomers are investigated in aqueous solutions. It is shown that exchange dynamics can be controlled by mixing different types of monomers. This tunability widens the scope in their design as biomaterials.\u3c/p\u3

Consequences of dispersity on the self-assembly of ABA-Type amphiphilic block co-oligomers

\u3cp\u3eIntriguingly, little is known about the impact of dispersity on the crystallization driven self-assembly (CDSA) of amphiphilic block copolymers in aqueous media. Here, we investigate the influence of dispersity on the CDSA of ABA-type amphiphilic block co-oligomers (ABCOs). Two pairs of ABCOs are synthesized comprising discrete ( Đ = 1.00) or disperse ( Đ = 1.20) isotactic l-lactic acid 16-mers as the semicrystalline hydrophobic block and either oligo(ethylene glycol) methyl ether (MeOoEG) or oligo(tetraethylene glycol succinate) (oTEGSuc) as the discrete hydrophilic block. Self-assembly studies in water with 10% THF reveal uniform nanofibers/2D sheets for the discrete oligomers, but such structural regularity is largely compromised in the disperse oligomers. The results are corroborated by sharp melting transitions in both solution and bulk for the discrete ABCOs, unlike their disperse analogues that show a lack of crystallization. Interestingly, the discrete MeOoEG-LLA oligomer reveals crystallization driven gelation, illustrating the contrasting differences between the discrete oligomers and their disperse counterparts. \u3c/p\u3

Supramolecular polymerisation in water; Elucidating the role of hydrophobic and hydrogen-bond interactions

\u3cp\u3eUnderstanding the self-assembly of small molecules in water is crucial for the development of responsive, biocompatible soft materials. Here, a family of benzene-1,3,5-tricarboxamide (BTA) derivatives that comprise a BTA moiety connected to an amphiphilic chain is synthesised with the aim to elucidate the role of hydrophobic and hydrogen-bonding interactions in the self-assembly of these BTAs. The amphiphilic chain consists of an alkyl chain with a length of 10, 11, or 12 methylene units, connected to a tetraethylene glycol (at the periphery). The results show that an undecyl spacer is the minimum length required for these BTAs to self-assemble into supramolecular polymers. Interestingly, exchange studies reveal only minor differences in exchange rates between BTAs containing undecyl or dodecyl spacers. Additionally, IR spectroscopy provides the first experimental evidence that hydrogen-bonding is operative and contributes to the stabilisation of the supramolecular polymers in water.\u3c/p\u3

Supramolecular modification of a sequence-controlled collagen-mimicking polymer

\u3cp\u3eStructurally and functionally well-defined recombinant proteins are an interesting class of sequence-controlled macromolecules to which different crosslinking chemistries can be applied to tune their biological properties. Herein, we take advantage of a 571-residue recombinant peptide based on human collagen type I (RCPhC1), which we functionalized with supramolecular 4-fold hydrogen bonding ureido-pyrimidinone (UPy) moieties. By grafting supramolecular UPy moieties onto the backbone of RCPhC1 (UPy-RCPhC1), increased control over the polymer structure, assembly, gelation, and mechanical properties was achieved. In addition, by increasing the degree of UPy functionalization on RCPhC1, cardiomyocyte progenitor cells were cultured on soft (?26 kPa) versus stiff (?68-190 kPa) UPy-RCPhC1 hydrogels. Interestingly, increased stress fiber formation, focal adhesions, and proliferation were observed on stiffer compared to softer substrates, owing to the formation of stronger cell-material interactions. In conclusion, a bioinspired hydrogel material was designed by a combination of two well-known natural components, i.e., a protein as sequence-controlled polymer and UPy units inspired on nucleobases.\u3c/p\u3