Logic-Gated Modulation of Cell Migration via Mesoscale Mechanical Uncaging Effects

Mesoscopic objects ranging from molecular machinery to cells are prevalent in nature. Unlike atomic and nanoscopic objects that do not have pronounced mechanical properties due to their small sizes, mesoscale substances demonstrate their unique mechanical features that can interfere with cell functions, particularly those with a mechanical nature such as cell migrations. Here, we demonstrate mechanical caging/uncaging effects in a DNA origami nanospring system that precisely controls cancer cell migrations. By leveraging DNA as a programming language, our work demonstrates the creation of logic gates (Boolean AND and OR gates) responsive to various miRNA inputs, resulting in mechanical and structural changes in DNA origami nanosprings serving as processors, which uncage the arginyl-glycyl-aspartate (RGD) ligands to interact with integrins on the cell membrane surface. The mechanical uncaging effect inhibits the migration of cancer cells. The strategy can be readily harnessed for targeted drug delivery with minimal off-target effects. Our proof-of-concept mesoscale DNA origami self-assembly highlights the potential for exquisite multimodal control of mechanical functions of cells with future applications in synthetic biology and precision medicine.