DNA-based Transmembrane Receptor-mediated Contact-dependent Signal Transduction between Artificial Cells

Developing artificial and scalable molecular platforms is crucial in engineering multicellular communication networks. In this study, we present an amphipathic DNA-based transmembrane receptor-mediated artificial intercellular communication and signal transduction system. We engineered intercellular communication between lipid vesicles, leveraging the programmability of DNA nanotechnology. The artificial communication system presented here is composed of ssDNA and dsDNA. The interaction between ligand-receptors and receptors-receptors is acquired by DNA hybridization between complementary DNA strands. Signal transmission between the lipid vesicles is triggered by an internal input in the sender, transforming DNA-based receptors (1. intracellular reception) to transmit the signal information to the receptors on the receiver (2. intercellular reception), forming an oligomer spanning through two lipid bilayers (3. transduction). The intracellular oligomer within the receiver can further recruit the internal subunits to release a DNA output signal in the receiver (4. response). The cellular communication is specifically designed to compartmentalize the input ligand in the intracellular environment so that signaling can occur upon physical contact between artificial cells as a selective means. With DNA nanotechnology programmed in the synthetic lipid vesicles, our artificial intercellular signal transduction system can be further expanded and exploited in more complex bioinspired multicellular communication networks.