A dual-mode aggregative host:guest indicator displacement sensing system has been created for the detection of trimethylated peptides and determination of histone demethylase activity. The combination of selective recognition of suitably sized trimethylammonium salts and reversible lipophilic aggregation of the host:guest complex provides a unique quenching mechanism that is not only dependent on affinity for sensitivity but the lipophilicity of the indicator. In addition, aggregation can be controlled by the application of chaotropic anions in the mixture, allowing a second level of discrimination between hard lysine groups and softer trimethyllysines.