Peters, E.; Tanase, D. A.; Di Michele, L.; Rubio-Sanchez, R.

Biological cells use cations as signalling messengers to regulate a variety of responses. Linking cations to the functionality of synthetic membranes is thus crucial to engineering advanced biomimetic agents, such as synthetic cells. Here, we introduce bio-inspired DNA-based receptors that exploit non-canonical G-quadruplexes for cation-actuated structural and functional responses in synthetic lipid membranes. Membrane confinement grants cation-dependent control over receptor assembly and, when supplemented with hemin co-factors, their peroxidase DNAzyme activity. Cation-mediated control extends to receptor lateral distribution to localise DNA-based catalysis within phase-separated membranes domains of model synthetic cells, imitating the localisation of multimeric membrane complexes to signalling hubs in living cells. Our strategy paves the way for engineering cation-responsive pathways for sensing, signalling, and communication in synthetic cellular systems.