Polysaccharides present in the glycocalyx and extracellular matrix are highly important for a multitude of functions. Oligo- and polysaccharides-based biomaterials are being developed to mimic the ...glycocalyx, but the spatial functionalization of these polysaccharides represents a major challenge. In this paper, a series of benzene-1,3,5-tricarboxamide (BTA) based supramolecular monomers is designed and synthesized with mono- (BTA-β-d-glucose; BTA-Glc and BTA-α-d-mannose; BTA-Man) or disaccharides (BTA-β-d-cellobiose; BTA-Cel) at their periphery or a monosaccharide (BTA-OEG4-α-d-mannose; BTA-OEG4-Man) at the end of a tetraethylene glycol linker. These glycosylated BTAs have been used to generate supramolecular assemblies and it is shown that the nature of the carbohydrate appendage is crucial for the supramolecular (co)polymerization behavior. BTA-Glc and BTA-Man are shown to assemble into micrometers long 1D (bundled) fibers with opposite helicities, whereas BTA-Cel and BTA-OEG4-Man formed small spherical micelles. The latter two monomers are used in a copolymerization approach with BTA-Glc, BTA-Man, or ethylene glycol BTA (BTA-OEG4) to give 1D fibers with BTA-Cel or BTA-OEG4-Man incorporated. Consequently, the carbohydrate appendage influences both the assembly behavior and the internal order. Using this approach it is possible to create 1D-fibers with adjustable saccharide densities exhibiting tailored dynamic exchange profiles. Furthermore, hydrogels with tunable mechanical properties can be achieved, opening up possibilities for the development of multicomponent functional biomaterials.
In biology, polymorphism is a well-known phenomenon by which a discrete biomacromolecule can adopt multiple specific conformations in response to its environment. The controlled incorporation of ...polymorphism into noncovalent aqueous assemblies of synthetic small molecules is an important step toward the development of bioinspired responsive materials. Herein, we report on a family of carboxylic acid functionalized water-soluble benzene-1,3,5-tricarboxamides (BTAs) that self-assemble in water to form one-dimensional fibers, membranes, and hollow nanotubes. Interestingly, one of the BTAs with the optimized position of the carboxylic group in the hydrophobic domain yields nanotubes that undergo reversible temperature-dependent dynamic reorganizations. SAXS and Cryo-TEM data show the formation of elongated, well-ordered nanotubes at elevated temperatures. At these temperatures, increased dynamics, as measured by hydrogen–deuterium exchange, provide enough flexibility to the system to form well-defined nanotube structures with apparently defect-free tube walls. Without this flexibility, the assemblies are frozen into a variety of structures that are very similar at the supramolecular level, but less defined at the mesoscopic level.
Supramolecular assembly affords the development of a wide range of polypeptide-based biomaterials for drug delivery and nanomedicine. However, there remains a need to develop a platform for the rapid ...synthesis and study of diverse polypeptide-based materials without the need for employing complex chemistries. Herein, we develop a versatile strategy for creating polypeptide-based materials using polyphenols that display multiple synergistic cross-linking interactions with different polypeptide side groups. We evaluated the diverse interactions operating within these polypeptide–polyphenol networks via binding affinity, thermodynamics, and molecular docking studies and found that positively charged polypeptides (K a of ∼2 × 104 M–1) and polyproline (K a of ∼2 × 106 M–1) exhibited stronger interactions with polyphenols than other amino acids (K a of ∼2 × 103 M–1). Free-standing particles (capsules) were obtained from different homopolypeptides using a template-mediated strategy. The properties of the capsules varied with the homopolypeptide used, for example, positively charged polypeptides produced thicker shell walls (120 nm) with reduced permeability and involved multiple interactions (i.e., electrostatic and hydrogen), whereas uncharged polypeptides generated thinner (10 nm) and more permeable shell walls due to the dominant hydrophobic interactions. Polyarginine imparted cell penetration and endosomal escape properties to the polyarginine–tannic acid capsules, enabling enhanced delivery of the drug doxorubicin (2.5 times higher intracellular fluorescence after 24 h) and a corresponding higher cell death in vitro when compared with polyproline–tannic acid capsules. The ability to readily complex polyphenols with different types of polypeptides highlights that a wide range of functional materials can be generated for various applications.
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.
Biomimetic, strain‐stiffening materials were made through self‐assembly and covalent fixation of small bisurea bolaamphiphile building blocks to form fibrous hydrogels. These gels are able to stiffen by an order of magnitude in response to applied stress.
The development of fluorescence labeling techniques has attracted widespread interest in various fields, including biomedical science as it can facilitate high‐resolution imaging and the ...spatiotemporal understanding of various biological processes. We report a supramolecular fluorescence labeling strategy using luminescent metal‐phenolic networks (MPNs) constructed from metal ions, phenolic ligands, and common and commercially available dyes. The rapid labeling process (<5 min) produces ultrathin coatings (≈10 nm) on diverse particles (e.g., organic, inorganic, and biological entities) with customized luminescence (e.g., red, blue, multichromatic, and white light) simply through the selection of fluorophores. The fluorescent coatings are stable at pH values from 1 to 8 and in complex biological media owing to the dominant π interactions between the dyes and MPNs. These coatings exhibit negligible cytotoxicity and their strong fluorescence is retained even when internalized into intracellular compartments. This strategy is expected to provide a versatile approach for fluorescence labeling with potential in diverse fields across the physical and life sciences.
A supramolecular fluorescence labeling strategy is established using luminescent metal‐phenolic networks constructed from metal ions, phenolic ligands, and dye molecules. Tunable and customized luminescence (e.g., red, blue, multichromatic, and white light) is achieved on inorganic, organic, and biological particles, with potential applications in the physical and life sciences.
Patchy nanoparticles featuring tunable surface domains with spatial and chemical specificity are of fundamental interest, especially for creating three-dimensional (3D) colloidal structures. Guided ...assembly and regioselective conjugation of polymers have been widely used to manipulate such topography on nanoparticles; however, the processes require presynthesized specialized polymer chains and elaborate assembly conditions. Here, we show how small molecules can form 3D patches in aqueous environments in a single step. The patch features (e.g., size, number, conformation, and stereoselectivity) are modulated by a self-polymerizable aromatic dithiol and comixed ligands, which indicates an autonomous assembly mechanism involving covalent polymerization and supramolecular assembly. Moreover, this method is independent of the underlying nanoparticle material and dimension, offering a streamlined and powerful toolset to design heterogeneous patches on the nanoscale.
Nature 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.
Intriguingly, 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.
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