Directing\nNanoparticle Organization in Response to\nDiverse Chemical Inputs

Signaling\ncascades are crucial for transducing stimuli in biological\nsystems, enabling multiple stimuli to regulate a downstream target\nwith precisely controlled timing and amplifying signals through a\nseries of intermediary reactions. Developing a robust signaling system\nwith such capabilities would be pivotal for programming complex behaviors\nin synthetic DNA-based molecular devices. However, although “software”\nsuch as nucleic acid circuits could potentially be harnessed to relay\nsignals to DNA-based nanostructure hardware, such explorations have\nbeen limited. Here, we develop a platform for transducing a variety\nof stimuli via messenger-mediated reactions to regulate the release\nand reloading of gold nanoparticles (AuNPs) in a 3D DNA framework.\nIn the first step, an in vitro transcription circuit is engineered\nto sense and amplify chemical stimuli, including arbitrary DNA sequences\nand proteins, producing RNA. In the second step, the RNA releases\nthe DNA-coated AuNPs from the DNA framework via a strand displacement\nreaction. AuNP reloading is controlled by a separate step driven by\ndegradation of the RNA. Our platform holds promise for applications\nrequiring dynamic multiagent control over DNA-based devices, offering\na versatile tool for advanced molecular device engineering.