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Cargo-selective membrane transport with DNA nanopores

Cargo-selective membrane transport with DNA nanopores

Stefan Howorka (ORCID: 0000-0002-6527-2846)
  • Grant DOI 10.55776/P30368
  • Funding program Principal Investigator Projects
  • Status ended
  • Start October 1, 2017
  • End September 30, 2021
  • Funding amount € 403,039

Disciplines

Biology (20%); Chemistry (50%); Nanotechnology (30%)

Keywords

    Chemical Biology, Nucleic Acids Chemistry, Macromolecular Chemistry, Protein Chemistry, Bioaffinity, Single Molecule Biophysics

Abstract Final report

This project deals with molecular transport processes that play an important role in biology and biotechnology. Transport across membrane barriers occurs when biomolecules are shuttled out of or into biological cells or when pharmaceutical compounds are purified with porous filtration membranes. The transport process studied in the project is mediated via small pore with a width of a few nanometers. Movement of molecules through these small openings is unique and different to microscale or macroscale systems in several ways. First, a pore with a narrow opening can impose a size limit for molecule to be transported. Second, inside a pore, a biomolecules can be spatially confined and temporarily captured. Third, the small length scale can lead to frequent interactions between the biomolecule and the pore wall. The transport type studied in this project is also unique in that the pores carry internal nanoscale affinity tracks. The tracks specifically recognize molecular cargo and thereby enable that only target molecules can pass the pore. Our project will provide a step-change in understanding of this transport process. It will overcome the current shortage of knowledge of how pore dimensions influence how fast or how specific molecules are transported. To realize the projects aim, our approach will combine experiments and mathematical simulations. We expect that our new scientific insight will help in the rational design of nanoporous purification membranes or nanopore-based devices such as biosensors.

This project has explored molecular transport processes that play an important role in biology and biotechnology. Transport across membrane barriers occurs when biomolecules are shuttled out of or into biological cells or when pharmaceutical compounds are purified with porous filtration membranes. The transport process studied in the project was mediated within small hollow pore of a width of a few nanometres. Movement of molecules through these small openings is unique and different to microscale or macroscale systems in several ways. (i) A pore with a narrow opening can impose a size limit for molecule to be transported. (ii) Inside a pore, biomolecules can be spatially confined and temporarily captured. (iii) The small length scale can lead to frequent interactions between the biomolecule and the pore wall. The transport type studied in this project was (iv) also unique in that the pores carry internal nanoscale affinity tracks. The tracks specifically recognize molecular cargo and thereby enable that only target molecules can pass the pore. To drastically improve these transport processes, our project has created the nanoscale pores of tuneable size and equipped them with affinity tracks. The passage of cargo was also followed via single-molecule analysis. Furthermore, a mathematical model of cargo transport was developed to generalise the experimental findings. Our new scientific insight will help in the rational design of nanoporous purification membranes or nanopore-based devices such as biosensors.

Research institution(s)
  • Technische Universität Wien - 14%
  • Universität Linz - 86%
Project participants
  • Clemens Heitzinger, Technische Universität Wien , associated research partner

Research Output

  • 53 Citations
  • 6 Publications
Publications
  • 2021
    Title Protein Transport through Nanopores Illuminated by Long-Time-Scale Simulations
    DOI 10.1021/acsnano.1c01078
    Type Journal Article
    Author Mitscha-Baude G
    Journal ACS Nano
    Pages 9900-9912
    Link Publication
  • 2019
    Title Structural and Functional Stability of DNA Nanopores in Biological Media
    DOI 10.3390/nano9040490
    Type Journal Article
    Author Burns J
    Journal Nanomaterials
    Pages 490
    Link Publication
  • 2018
    Title Tunable DNA Hybridization Enables Spatially and Temporally Controlled Surface-Anchoring of Biomolecular Cargo
    DOI 10.1021/acs.langmuir.8b01942
    Type Journal Article
    Author Hager R
    Journal Langmuir
    Pages 15021-15027
    Link Publication
  • 2023
    Title Molecular Recognition in Confined Space Elucidated with DNA Nanopores and Single-Molecule Force Microscopy.
    DOI 10.1021/acs.nanolett.3c00743
    Type Journal Article
    Author Suh Sh
    Journal Nano letters
    Pages 4439-4447
  • 2023
    Title Facilated cargo DNA transport studied with AFM
    Type PhD Thesis
    Author Saanfor Hubert Suh
  • 2022
    Title Triggered Assembly of a DNA-Based Membrane Channel
    DOI 10.1021/jacs.1c06598
    Type Journal Article
    Author Lanphere C
    Journal Journal of the American Chemical Society
    Pages 4333-4344
    Link Publication

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