DNA-Based Dynamic Mimicry of Membrane Proteins for Programming Adaptive Cellular Interactions

Cells sense and respond to the external environment, mainly through proteins presented on the membrane where their expression and conformation are dynamically regulated via intracellular programs. Here, we engineer a cell-surface nanoarchitecture that realizes molecular-recognition-initiated DNA assembly to mimic the dynamic behavior of membrane proteins, enabling the manipulation of cellular interaction in response to environmental changes. Our results show that this membrane-anchored DNA nanoarchitecture can be specifically activated by cell-responsive signals to external stimulation. Accordingly, multiple functional modules can be assembled onto the membrane to equip the cell with cell-type-specific binding and killing. This system is expected to offer a new paradigm for engineering therapeutic cells with customized sensing/response pathways.