The bottom-up assembly of synthetic cell systems capable of recapitulating biological functions has become a means to understand living matter by construction. The integration of biomolecular components into active, cell-sized, genetically programmed compartments remains, however, a major bottleneck for building synthetic cells. A primary feature of real cells is their ability to actively interact with their surroundings, particularly in stressed conditions. Here, we construct a synthetic cell equipped with an inducible genetic circuit that responds to changes in osmotic pressure through the mechanosensitive channel MscL. Liposomes loaded with an E. coli cell-free transcription-translation (TXTL) system are induced with IPTG when exposed to hypo-osmotic solution, resulting in the expression of a bacterial cytoskeletal protein (MreB). MreB associates with the membrane to generate a cortex-like structure. Our work provides the first example of molecular integration that couples mechanosensitivity, gene expression, and self-assembly at the inner membrane of synthetic cells.