LAUSR

The DNA strand displacement reaction has had sustained scientific interest in building complicated nucleic acid-based net-works. However, extending the fundamental mechanism to more diverse biomolecules in a complex environment remains challenging. Aptamers bind with targeted biomolecules with high affinity and selectivity, thus offering a promising route to link the powers of nucleic acid with diverse cues. Here, we describe three methods that allow facile and efficient displace-ment reaction of aptamer from the living cell surface using complement DNA (cDNA), toehold-labeled cDNA (tcDNA), and single-stranded binding protein (SSB). The kinetics of DNA strand displacement reaction is severely affected by complex physicochemical properties of the natural membrane. Toehold-mediated and SSB-mediated aptamer displacement exhibit-ed significantly enhanced kinetics, and they completely removed the aptamer quickly to avoid a false signal caused by ap-tamer internalization. Because of its simplicity, aptamer displacement enabled detection of membrane protein post-translation and improved selection efficiency of cell-SELEX.