Artificial Gap Junctional Channel Inhibiting the Proliferation of Hepatocellular Carcinoma Cells

Gap junctions play a crucial role in intercellular communication, participating in both physiological and pathological processes. Although artificial gap junctions have been developed, their physiological functions beyond basic intercellular communication remain largely unexplored. Herein, we report a functional artificial gap junctional channel system constructed via electrostatic co-assembly of an amphiphilic transmembrane channel and a hydrophilic extracellular channel. The efficient ion transport capability of the amphiphilic channel, coupled with the extensive aggregation of the hydrophilic module within the intercellular gap, enables the formation of stable intercellular junctions. Similar to natural gap junctions, these artificial channels not only mediate intercellular ion transport but also induce G1 phase cell cycle arrest and inhibit the proliferation of hepatocellular carcinoma cells. This work provides a new strategy for intervening in cell-cell communication and offers a potential therapeutic avenue for cancer and gap junction-related diseases.