Stimuli‐Responsive Prototissues via DNA‐Mediated Self‐Assembly of Polymer Giant Unilamellar Vesicles

Gaining insight into the complex functions of tissues, which involve communicating cell types, by utilizing materials that mimic the properties of real tissue, is an important step in developing advanced biomedical applications. However, building 3D networks of interconnected protocells capable of chemical information processing and collective output remains a challenge. Herein, the construction of a prototissue based on the DNA‐mediated assembly of polymeric giant unilamellar vesicles (pGUVs) are presented with differential sensitivity, forming a multicompartment communicating system. One set of pGUVs hosts microgels as artificial Mg2+ storage organelles, which can be triggered to release their Mg2+ by pH changes in the environment. The downstream linked set of protocells contains a Mg2+ sensitive dye that responds to the Mg2+ signal. The density of complementary DNA strands on the surface of the respective pGUVs determines not only the size of the pGUV ensemble but also modulates sensitivity toward magnesium. Moreover, Mg2+ signaling to downstream protocells loaded with monomeric actin induces the in situ formation of an artificial cytoskeleton. Overall, through the clustering of protocells hosting distinct artificial organelles with controlled architecture, such unique prototissues that mimic intratissue communication generate new prospects in using advanced functional materials for multi‐step catalysis and biomedicine. Stimuli‐responsive prototissues are constructed by DNA‐mediated assembly of polymeric giant unilamellar vesicles (pGUVs) harboring distinct stimuli‐responsive artificial organelles and biomolecules. Upon acidification of the environment, Mg2+‐storing organelles in one pGUV population release their content into the protocell lumen. The released Mg2+ acts as second messenger to stimulate either fluorescence or the in situ formation of actin filaments in downstream protocells.