Lanphere, Conor;
Ciccone, Jonah;
Dorey, Adam;
Hagleitner-Ertuğrul, Nora;
Knyazev, Denis;
Haider, Shozeb;
Howorka, Stefan;
(2022)
Triggered Assembly of a DNA-Based Membrane Channel.
Journal of the American Chemical Society
, 144
(10)
pp. 4333-4344.
10.1021/jacs.1c06598.
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Abstract
Chemistry is in a powerful position to synthetically replicate biomolecular structures. Adding functional complexity is key to increase the biomimetics' value for science and technology yet is difficult to achieve with poorly controlled building materials. Here, we use defined DNA blocks to rationally design a triggerable synthetic nanopore that integrates multiple functions of biological membrane proteins. Soluble triggers bind via molecular recognition to the nanopore components changing their structure and membrane position, which controls the assembly into a defined channel for efficient transmembrane cargo transport. Using ensemble, single-molecule, and simulation analysis, our activatable pore provides insight into the kinetics and structural dynamics of DNA assembly at the membrane interface. The triggered channel advances functional DNA nanotechnology and synthetic biology and will guide the design of controlled nanodevices for sensing, cell biological research, and drug delivery.
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