Dynamic regulation of intermolecular interactions is essential for the creation of dynamic supramolecular materials with lifelike self-regulating functions. Yet specific ion effect, which is known to possess potent effect on intermolecular interactions, has remained unexplored for such a purpose. Here, we demonstrate our access to dynamic self-assembly of supramolecular hydrogels by orchestrating the Hofmeister effect through a simple enzymatic reaction. The involved gelators containing carboxylate moieties self-assemble into hydrogel (Gel1) at acidic pH and dissolve at basic pH. We surprisingly find that the dissolved gelators at basic pH can be driven to self-assemble into hydrogel (Gel2) by kosmotropic ions through the disruption of gelator–water interactions. By coupling to the enzymatic hydrolysis of urea, Gel1 gradually disintegrates over time because of the production of basic NH3. However, interestingly, with the accumulation of kosmotropic ions, NH4+ and CO32−, the dissolved gelators are driven to self-assemble into Gel2, realizing a self-regulating gel–sol–gel transition process. The transition rate and stiffness of Gel2 are tunable by adjusting the concentrations of urea or urease. This work may shed light on the creation of lifelike self-regulating supramolecular materials using Hofmeister effect for many enticing applications such as ion-programmed biosensing and drug delivery.

Cells execute mesmerizing functions using supramolecular polymers (SPs) formed through the self-assembly of biological precursors. Integration of the vast array of synthetic SPs with living cells would offer a powerful way to remold cellular functions and bridge the gap between synthetic materials and the biological realm, yet remains a challenge because of the lack of robust abiotic SP systems that can be triggered to self-assemble inside cells. Here, we report how fully abiotic SPs can be synthesized inside living cells via an organocatalysis-responsive self-assembly strategy, and how the in situ-generated SPs are capable of interfering and can interfere with cellular functions. The incorporation of a nucleophilic organocatalyst (CAT) into living cells accelerates the intracellular conversion of hydrazide (H) and aldehyde-derived precursors (A) to hydrazone-based monomers (HA3) that locally self-assemble into SPs. Interestingly, the in situ-generated SPs possess ignorable effects on cell viability and proliferation but remarkably hinder cell migration. Furthermore, the presence of SPs is found to retard intracellular diffusion and alter the organization of the actin cytoskeleton, both of which are suggested to be responsible for the hindered cellular migration. In considering the vastly wide range of synthetic SPs, tremendous non-natural cellular functionalities can be obtained by in situ-synthesizing SPs.