Abstract
Synthetic tissues built from communicating aqueous droplets offer potential applications in biotechnology, however, controlled release of their contents has not been achieved. Here we construct two-droplet synthetic tissue modules that function in an aqueous environment. One droplet contains a cell-free protein synthesis system and a prodrug-activating enzyme and the other a small-molecule prodrug analog. When a Zn2+-sensitive protein pore is made in the first droplet, it allows the prodrug to migrate from the second droplet and become activated by the enzyme. With Zn2+ in the external medium, the activated molecule is retained in the module until it is released on-demand by a divalent cation chelator. The module is constructed in such a manner that one or more, potentially with different properties, might be incorporated into extended synthetic tissues, including patterned materials generated by 3D-printing. Such modules will thereby increase the sophistication of synthetic tissues for applications including controlled multidrug delivery.
Highlights
Synthetic tissues built from communicating aqueous droplets offer potential applications in biotechnology, controlled release of their contents has not been achieved
We demonstrated controlled synthesis of αHL from a light-activated DNA template, which mediated the movement of ions and small molecules across a DIB21,22
By contrast, when ZnCl2 was in the neighbouring droplet, we observed
Summary
Synthetic tissues built from communicating aqueous droplets offer potential applications in biotechnology, controlled release of their contents has not been achieved. A vital development would be the ability to controllably permeabilize the external membranes, while keeping the internal membranes permeable This would allow reactions to occur internally, before release of the products upon demand. TRIMEB has been used with multicompartment structures assembled from vesicles, to block leakage to the external environment and allow transfer across between the compartments[20] In this case, transfer was measured over only 10 min, no internal reactions were performed, and any leakage to the external solution was not assayed. The release of small molecules from multicompartment lipid-bounded structures into an external aqueous environment has been demonstrated with αHL generated by IVTT23
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