Highly Synergistic Properties of Multicomponent Hydrogels Thanks to Cooperative Nucleopeptide Assemblies

Supramolecular materials have drawn much attention inthe pastyears, particularly because of their great versatility in terms ofstructures, organization, and types of nano-objects they can form.Among them, amino acid and peptide derivatives are biomolecules extensivelyused thanks to their inherent properties and applicability for biologicaland health applications. Their exceptional abilities to self-assemblehave been harnessed to create a myriad of objects and materials, includinghydrogels. However, the use of one and only one molecule (i.e., monocomponent)is the widely reported approach which is of great interest in termsof simplicity of use, but it has numerous limitations in terms ofproperties. To tackle these issues, the multicomponent approach isa promising strategy, even if challenging, for designing low-molecular-weightmolecules able to interact with each other to create new assembliesand new properties not achievable with a single compound. In thiscontext, we report herein on the design, synthesis, and multiscaleanalysis of an original series of nucleopeptides, i.e., comprisingboth peptide and DNA-nucleobase moieties linked covalently. Thanksto their dual nature, these nucleopeptides are able to co-assemblewhen complementary nucleobase moieties interact intermolecularly viahydrogen bonding and pi-stacking interactions, leading to impressivesynergistic effects, which result in mechanical properties improvedby more than 270,000% (with stiffness up to >700 kPa) and self-assemblyabilities by similar to 280%. To decipher the structure/property relationships,a comprehensive multiscale analysis approach (including rheology,fluorescence, cryo-scanning electron microscopy, transmission electronmicroscopy, Fourier transform infrared spectroscopy, circular dichroism,nuclear magnetic resonance, and high-resolution magic angle spinning)has been carried out to understand the impact of nucleobases on thesupramolecular assembly process and the subsequent formation of nanoobjects,three-dimensional architectures of the hydrogel scaffold, and theresulting physicochemical and mechanical properties of these highlysynergistic nucleopeptide assemblies.

Automated summary

Supramolecular materials, such as amino acid and peptide derivatives, are versatile in terms of structures and forms they can create. The use of a multicomponent approach, combining peptide and DNA-nucleobase moieties, can lead to impressive synergistic effects, improving mechanical properties and self-assembly abilities. A comprehensive multiscale analysis has been carried out to understand the impact of nucleobases on the supramolecular assembly process and the resulting properties of these nucleopeptide assemblies.