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Fabrication of cytotoxic mirror image nanopores

Author

Listed:
  • Neilah Firzan CA

    (Rajiv Gandhi Centre for Biotechnology
    Manipal Academy of Higher Education)

  • Kalyanashis Jana

    (Constructor University)

  • Sreelakshmi Radhakrishnan

    (CSIR - National Institute for Interdisciplinary Science and Technology (NIIST)
    Academy of Scientific and Innovative Research (AcSIR))

  • Rifat Aara

    (Centre for Human Genetics)

  • Mubeena S

    (Centre for Human Genetics)

  • Radhika Nair

    (Centre for Human Genetics)

  • Harsha Bajaj

    (CSIR - National Institute for Interdisciplinary Science and Technology (NIIST)
    Academy of Scientific and Innovative Research (AcSIR))

  • Ulrich Kleinekathöfer

    (Constructor University)

  • Kozhinjampara R. Mahendran

    (Rajiv Gandhi Centre for Biotechnology)

Abstract

Synthetic nanopores composed of mirror-image peptides have been reported, but not fully functional mirror-image pores. Here, we construct a monodisperse mirror-image nanopore, DpPorA and characterise its functional properties. Importantly, we alter the charge pattern and assemble a superior mirror-image pore with enhanced conductance and selectivity under different salt conditions. This pore is used for single-molecule sensing of structurally divergent biomolecules, including peptides, PEGylated polypeptides, full-length alpha-synuclein protein and cyclic sugars. Molecular dynamics simulations confirm these DpPorA are exact mirror-images of LpPorA, further revealing their structurally stable conformation. Fluorescence imaging of giant vesicles reconstituted with mirror-image peptides reveals the formation of large flexible pores facilitating size-dependent molecular transport. To explore biomedical applications, the differential cytotoxic effect of mirror-image peptides and their fluorescently tagged forms on cancer cells demonstrates a significant effect on membrane disruption and cell viability, as opposed to no effect on normal cells. We emphasize that this class of mirror-image pores can advance the development of molecular sensors and therapeutics.

Suggested Citation

  • Neilah Firzan CA & Kalyanashis Jana & Sreelakshmi Radhakrishnan & Rifat Aara & Mubeena S & Radhika Nair & Harsha Bajaj & Ulrich Kleinekathöfer & Kozhinjampara R. Mahendran, 2025. "Fabrication of cytotoxic mirror image nanopores," Nature Communications, Nature, vol. 16(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-64025-6
    DOI: 10.1038/s41467-025-64025-6
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