Nature Chemistry, Published online: 18 August 2026; doi:10.1038/s41557-026-02225-3 Constructing protocell networks with spatial dynamics remains a central challenge in colloidal systems chemistry. Now, binary populations of enzyme-containing protocells with different membrane wettability have been shown to spontaneously segregate in phase-separated media. Enzyme-mediated signals induce reversible phase compatibility, enabling selective protocell recruitment and dispatchment, and the construction of cytomimetic networks with self-regulated spatiotemporal order.