@article{17441bd433574131bad6bb6179fe8696,
title = "Electro-mechanical conductance modulation of a nanopore using a removable gate",
abstract = "Ion channels form the basis of information processing in living cells by facilitating the exchange of electrical signals across and along cellular membranes. Applying the same principles to man-made systems requires the development of synthetic ion channels that can alter their conductance in response to a variety of external manipulations. By combining single-molecule electrical recordings with all-atom molecular dynamics simulations, we here demonstrate a hybrid nanopore system that allows for both a stepwise change of its conductance and a nonlinear current-voltage dependence. The conductance modulation is realized by using a short flexible peptide gate that carries opposite electric charge at its ends. We show that a constant transmembrane bias can position (and, in a later stage, remove) the peptide gate right at the most-sensitive sensing region of a biological nanopore FraC, thus partially blocking its channel and producing a stepwise change in the conductance. Increasing or decreasing the bias while having the peptide gate trapped in the pore stretches or compresses the peptide within the nanopore, thus modulating its conductance in a nonlinear but reproducible manner. We envision a range of applications of this removable-gate nanopore system, e.g. from an element of biological computing circuits to a test bed for probing the elasticity of intrinsically disordered proteins.",
keywords = "Biomimetic systems, Gating, Ion channel, Molecular dynamics, Protein sequencing",
author = "Shidi Zhao and Laura Restrepo-P{\'e}rez and Misha Soskine and Giovanni Maglia and Chirlmin Joo and Cees Dekker and Aleksei Aksimentiev",
note = "Funding Information: This work was supported by the National Institute of Health through grant nos. R01-HG007406 and P41-GM104601. The C.D. lab was further supported by the ERC Advanced Grant SynDiv (no. 669598). G.M., C.J, and C.D. were funded by the Foundation for Fundamental Research on Matter (FOM vrije programma, SMPS). L.R., C.J., and C.D. were funded by The Netherlands Organization of Scientific Research (NWO/OCW) as part of the Frontiers of the Nanoscience Program. The supercomputer time provided through XSEDE Allocation grant no. MCA05S028 and the Blue Waters petascale supercomputer system (UIUC). Funding Information: This work was supported by the National Institute of Health through grant nos. R01-HG007406 and P41-GM104601. The C.D. lab was further supported by the ERC Advanced Grant SynDiv (no. 669598). G.M., C.J, and C.D. were funded by the Foundation for Fundamental Research on Matter (FOM vrije programma, SMPS). L.R., C.J., and C.D. were funded by The Netherlands Organization of Scientific Research (NWO/ OCW) as part of the Frontiers of the Nanoscience Program. The supercomputer time provided through XSEDE Allocation grant no. MCA05S028 and the Blue Waters petascale supercomputer system (UIUC). Publisher Copyright: {\textcopyright} 2019 American Chemical Society.",
year = "2019",
month = feb,
day = "26",
doi = "10.1021/acsnano.8b09266",
language = "English",
volume = "13",
pages = "2398--2409",
journal = "ACS Nano",
issn = "1936-0851",
publisher = "American Chemical Society",
number = "2",
}