Abstract
Chemistry is ideally placed to replicate biomolecular structures with tuneable building materials. Of particular interest are molecular nanopores, which transport cargo across membranes, as in DNA sequencing. Advanced nanopores control transport in response to triggers, but this cannot be easily replicated with biogenic proteins. Here we use DNA nanotechnology to build a synthetic molecular gate that opens in response to a specific protein. The gate self-assembles from six DNA strands to form a bilayer-spanning pore, and a lid strand comprising a protein-binding DNA aptamer to block the channel entrance. Addition of the trigger protein, thrombin, selectively opens the gate and enables a 330-fold increase inw the transport rate of small-molecule cargo. The molecular gate incorporates in delivery vesicles to controllably release enclosed cytotoxic drugs and kill eukaryotic cells. The generically designed gate may be applied in biomedicine, biosensing or for building synthetic cells.
Highlights
Creating engineered or synthetic membrane channels is of interest in science and technology
We use DNA nanotechnology to build a synthetic molecular gate that opens in response to a specific protein
The molecular gate incorporates in delivery vesicles to controllably release enclosed cytotoxic drugs and kill eukaryotic cells
Summary
This advanced function could be used in biosensing approaches,[8] drug delivery systems,[9] or synthetic cell-like entities.[10] Adapting natural gates[11] for applications outside their biological remit is, difficult. We use DNA nanotechnology to build an artificial protein-regulated molecular gate for off-on switched transport of cytotoxic drugs. The outer dimensions of the molecular gate are approximately 13 5 5 nm
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