The on-demand delivery of drug molecules from nanoscale carriers with spatiotemporal control is a key challenge in modern medicine. Here we show that lipid bilayer vesicles (liposomes) can be triggered to release an encapsulated molecular cargo in response to an external control signal by employing an artificial transmembrane signal transduction mechanism. A synthetic signal transducer embedded in the lipid bilayer membrane acts as a switchable catalyst, catalyzing the formation of surfactant molecules inside the vesicle in response to a change in external pH. The surfactant permeabilizes the lipid bilayer membrane to facilitate release of an encapsulated hydrophilic cargo. In the absence of the pH control signal, the catalyst is inactive, and the cargo remains encapsulated within the vesicle.