Although the complexity of synthetic cells has continued to increase in recent years, chemical communication between protocell models and living organisms remains a key challenge in bottom-up synthetic biology and bioengineering. In this Review, we discuss how communication channels and modes of signal processing can be established between living cells and cytomimetic agents such as giant unilamellar lipid vesicles, proteinosomes, polysaccharidosomes, polymer-based giant vesicles and membrane-less coacervate micro-droplets. We describe three potential modes of chemical communication in consortia of synthetic and living cells based on mechanisms of distributed communication and signal processing, physical embodiment and nested communication, and network-based contact-dependent communication. We survey the potential for applying synthetic cell/living cell communication systems in biomedicine, including the in situ production of therapeutics and development of new bioreactors. Finally, we present a short summary of our findings.

The spontaneous assembly of nanoscale building blocks into continuous semipermeable membranes is a key requirement for the structuration of synthetic protocells.Engineering the functionality and programmability of these building units provides a step towards more complex cell-like entities with adaptive membrane properties. Inspired by the central role of protein (lectin)-carbohydrate interactions in cellular recognition and adhesion, we fabricate semipermeable polysaccharide-polymer microcapsules (polysaccharidosomes) with intrinsic lectinbinding properties. We employ amphiphilic polysaccharide-polymer membrane building blocks endowed with intrinsic bio-orthogonal lectin-glycan recognition sites to facilitate the reversible non-covalent docking of functionalized polymer or zeolitic nanoparticles on the polysaccharidosomes. We show that the programmed attachment of enzyme-loaded nanoparticles

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