A Diffusion-Based Synthetic Cell Communication Network Enabled by a Multitasking Deoxyribonucleic Acid Nanomachine

DNA-mediated synthetic cell communication enabling non-natural signaling and regulatory pathways is highly attractive but relies on direct cell contacts. Here, we report a diffusion-based synthetic cell communication capable of regulating migration behaviors of epithelial cell adhesion molecule (EpCAM)-overexpressed cancer cells in response to apoptosis events at distal sites. This synthetic cell communication network is enabled by a multitasking DNA nanomachine that not only mediates signal production, transmission, and regulation of cell migration but also amplifies signaling ligands in situ in response to specific receiver cells to overcome the signal attenuation during diffusion. Leveraging this diffusion-based synthetic cell communication network, we demonstrate the inhibition of cancer cell migrations in response to distal apoptosis events induced by an anticancer drug. Our system enriches current DNA nanotechnological tools for manipulating cellular interactions and function. It also directs a possible intervening strategy to reduce the invasiveness of cancer cells.