Sequential Control of Cellular Interactions Using Dynamic DNA Displacement

Intercellular interactions play a significant role in various complex biological processes, and their dysregulation promotes disease progression. To reveal the mechanisms of intercellular interactions without destroying basic life processes, it is necessary to mimic multicellular behaviors in vitro. However, the precise control of multicellular systems remains technically challenging owing to dynamic interactions. Here, we used DNA as a molecular lock and key to sequentially assemble and disassemble different cell clusters in a programmed way, regulating intercellular interactions. Tagging the surface of live cells with cholesterol-modified DNA enabled dynamical intercellular assemblies. By consecutively adding corresponding metaphorical locks (attaching DNA strands) and keys (detaching DNA strands), clusters of different cells could be sequentially formed. This strategy improved the capability of natural killer NK-92 cells to target tumor cells, improving the antitumor therapy efficacy. Our suggested approach allows dynamic regulation of intercellular interactions in complex cell systems and increases understanding of intercellular communication networks.