Where biology makes extensive use of signal-responsive chemical reaction networks to regulate various biochemical and assembly processes, translation of these principles to abiotic systems is still rare. Here, we report an aggregation process forming a supramolecular network held together by host-guest interactions, responsive to nucleophilic chemical signals through a chemical reaction-assembly cascade. In particular, we developed a signal induced switch between cucurbituril binary and ternary complexes with cationic bipyridine derivatives, where the charge on the bipyridine can be changed through an allylic substitution reaction with the nucleophilic signal. The kinetics of this reaction and the coupled aggregation process can be tuned using a range of biologically relevant nucleophilic signals. In addition, we developed a signal transducer to enable response to weakly nucleophilic signals. When applied to a multitopic bipyridine guest, reaction with the nucleophile signals leads to supramolecular network formation where the aggregation rates and final structure depend on the nucleophilicity of the signal. This work opens the door to new opportunities for signal responsive synthetic materials and interaction with biological systems.