Abstract
Synthetic DNA motors have great potential to mimic natural protein motors in cells but the operation of synthetic DNA motors in living cells remains challenging and has not been demonstrated. Here we report a DNAzyme motor that operates in living cells in response to a specific intracellular target. The whole motor system is constructed on a 20 nm gold nanoparticle (AuNP) decorated with hundreds of substrate strands serving as DNA tracks and dozens of DNAzyme molecules each silenced by a locking strand. Intracellular interaction of a target molecule with the motor system initiates the autonomous walking of the motor on the AuNP. An example DNAzyme motor responsive to a specific microRNA enables amplified detection of the specific microRNA in individual cancer cells. Activated by specific intracellular targets, these self-powered DNAzyme motors will have diverse applications in the control and modulation of biological functions.
Highlights
Synthetic DNA motors have great potential to mimic natural protein motors in cells but the operation of synthetic DNA motors in living cells remains challenging and has not been demonstrated
To operate in living cells, synthetic DNA motors must confront the following challenges: first, all components of the motor system, including the motor and its track, must be readily taken up by living cells; second, the operation of the motor must be initiated by specific molecules within the cells; third, the motor has to be self-powered to enable autonomous intracellular walking, because external addition of fuel DNA strands or protein enzymes is not desirable; the operation of the motor in living cells should be monitored in real time
We describe a strategy of constructing a DNAzyme motor system on a AuNP that meets all four requirements
Summary
Synthetic DNA motors have great potential to mimic natural protein motors in cells but the operation of synthetic DNA motors in living cells remains challenging and has not been demonstrated. We report a DNAzyme motor that operates in living cells in response to a specific intracellular target. To operate in living cells, synthetic DNA motors must confront the following challenges: first, all components of the motor system, including the motor and its track, must be readily taken up by living cells; second, the operation of the motor must be initiated by specific molecules within the cells; third, the motor has to be self-powered to enable autonomous intracellular walking, because external addition of fuel DNA strands or protein enzymes is not desirable; the operation of the motor in living cells should be monitored in real time. The operation of the DNAzyme motor is self-powered, because the autonomous walking of the motor along the AuNP is fueled by DNAzymecatalysed substrate cleavage. Each walking step of the motor results in an increase in fluorescence, allowing real-time imaging of the intracellular operation of the motor
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