No abstract

Self-assembly of small molecules in water to form nanofibers, besides generating sophisticated biomaterials, promises a simple system inside cells for regulating cellular processes. But lack of a convenient approach for studying the self-assembly of small molecules inside cells hinders the development of such systems. Here we report a method to image enzyme-triggered self-assembly of small molecules inside live cells. After linking a fluorophore to a self-assembly motif to make a precursor, we confirmed by 31P NMR and rheology that enzyme-triggered conversion of the precursor to a hydrogelator results in the formation of a hydrogel via self-assembly. The imaging contrast conferred by the nanofibers of the hydrogelators allowed the evaluation of intracellular self-assembly; the dynamics, and the localization of the nanofibers of the hydrogelators in live cells. This approach explores supramolecular chemistry inside cells and may lead to new insights, processes, or materials at the interface of chemistry and biology.

In this paper we report the conjugation of an aromatic moiety (pyrene (P), fluorene (F), or naphthalene (N)) to pentapeptides GAGAS (1), GVPVP (2), VPGVG (3), VTEEI (4), VYGGG (5), and YGFGG (6) to afford peptidic derivatives for exploring pentapeptide-based hydrogels as potential biomaterials. Most of these compounds (1F, 1P, 2F, 2P, 4F, 4P, 4N, 5F, 5N, 6F, 6P, and 6N) behave as molecular hydrogelators and can form hydrogels at minimum concentrations of gelation from 0.5 to 2.8 wt %. The fluorescence spectra of the hydrogels exhibit a significant red shift, indicating the interactions between the aromatic moieties in those hydrogels. The circular dichroism spectra indicate that the self-assembly of the hydrogelators affords helical or beta-sheet-like structures. Transmission and scanning electron microscopic examination reveals the nanofiber networks of these hydrogelators. In addition, rheological measurements show fair to excellent viscoelastic properties of these hydrogels. The balance of intermolecular aromatic-aromatic interactions and hydrogen bonds of these hydrogelators leads to their self-assembly in water and the formation of nanofibers as the matrixes of hydrogels. A total of 6 of these 18 pentapeptide derivatives--1N, 2N, 3F, 3P, 3N, and 5P--fail to form hydrogels under the conditions tested, likely due to unbalanced intermolecular interactions. This work suggests that aromatic-aromatic interactions are useful and favorable forces for creating molecular nanofibers and supramolecular hydrogels.