Membrane-Associated Biomolecules for Synthetic Cell Signalling.

Membrane-associated biomolecules, primarily proteins, are key enablers of communication, responsiveness, and complexity in natural living cells. Aiming to mimic these capabilities, there is growing interest in equipping bottom-up synthetic cells with membrane-associated biomolecular components. In this review, we focus on how proteins and nucleic acids have been associated with synthetic cell membranes, particularly lipid vesicles, to enable the transmission of signals across the membrane. We discuss strategies for anchoring these biomolecules into lipid bilayers and review how they can enable essential signalling mechanisms in synthetic cells, including cell tethering, the generation and fusion of vesicles, and signal transmission and transduction. We highlight how proteins offer native biological functionality, while nucleic acids may bring more modularity and control. Advancing this area will be essential for realising synthetic systems capable of studying natural communication mechanisms and unlocking applications in biosensing, therapeutics, and synthetic tissue engineering.