Spatial Control of Receptor Dimerization Using Programmable DNA Nanobridge

Receptor dimerization is an essential mechanism for the activation of most receptor tyrosine kinases by ligands. Thus, regulating the nanoscale spatial distribution of cell surface receptors is significant for studying both intracellular signaling pathways and cellular behavior. However, there are currently very limited methods for exploring the effects of modulating the spatial distribution of receptors on their function by using simple tools. Herein, we developed an aptamer-based double-stranded DNA bridge acting as "DNA nanobridge", which regulates receptor dimerization by changing the number of bases. On this basis, we confirmed that the different nanoscale arrangements of the receptor can influence receptor function and its downstream signals. Among them, the effect gradually changed from helping to activate to inhibiting as the length of DNA nanobridge increased. Hence, it can not only effectively inhibit receptor function and thus affect cellular behavior but also serve as a fine-tuning tool to get the desired signal activity. Our strategy is promising to provide insight into the action of receptors in cell biology from the perspective of spatial distribution.