Imaging enzyme-triggered self-assembly of small molecules inside live cells

Abstract

Self-assembly of small molecules in water to form nanofibres, 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 nanofibres of the hydrogelators allowed the evaluation of intracellular self-assembly, the dynamics and the localization of the nanofibres 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. Supramolecular interactions allow some small molecules to self-assemble into nanofibres and hydrogels in aqueous environments. Gaoet al.report a hydrogelator that forms fluorescent nanofibres within cells, leading to the visualization of their self-assembly at the endoplasmic reticulum.