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Optical tweezers-controlled hotspot for sensitive and reproducible surface-enhanced Raman spectroscopy characterization of native protein structures

Author

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  • Xin Dai

    (The Hong Kong University of Science and Technology
    Laboratory for Synthetic Chemistry and Chemical Biology, Health@InnoHK, Hong Kong Science Park)

  • Wenhao Fu

    (The Hong Kong University of Science and Technology)

  • Huanyu Chi

    (The Hong Kong University of Science and Technology)

  • Vince St. Dollente Mesias

    (The Hong Kong University of Science and Technology)

  • Hongni Zhu

    (The Hong Kong University of Science and Technology)

  • Cheuk Wai Leung

    (The Hong Kong University of Science and Technology)

  • Wei Liu

    (The University of Hong Kong)

  • Jinqing Huang

    (The Hong Kong University of Science and Technology)

Abstract

Surface-enhanced Raman spectroscopy (SERS) has emerged as a powerful tool to detect biomolecules in aqueous environments. However, it is challenging to identify protein structures at low concentrations, especially for the proteins existing in an equilibrium mixture of various conformations. Here, we develop an in situ optical tweezers-coupled Raman spectroscopy to visualize and control the hotspot between two Ag nanoparticle-coated silica beads, generating tunable and reproducible SERS enhancements with single-molecule level sensitivity. This dynamic SERS detection window is placed in a microfluidic flow chamber to detect the passing-by proteins, which precisely characterizes the structures of three globular proteins without perturbation to their native states. Moreover, it directly identifies the structural features of the transient species of alpha-synuclein among its predominant monomers at physiological concentration of 1 μM by reducing the ensemble averaging. Hence, this SERS platform holds the promise to resolve the structural details of dynamic, heterogeneous, and complex biological systems.

Suggested Citation

  • Xin Dai & Wenhao Fu & Huanyu Chi & Vince St. Dollente Mesias & Hongni Zhu & Cheuk Wai Leung & Wei Liu & Jinqing Huang, 2021. "Optical tweezers-controlled hotspot for sensitive and reproducible surface-enhanced Raman spectroscopy characterization of native protein structures," Nature Communications, Nature, vol. 12(1), pages 1-9, December.
  • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-21543-3
    DOI: 10.1038/s41467-021-21543-3
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    Cited by:

    1. Wenhao Fu & Huanyu Chi & Xin Dai & Hongni Zhu & Vince St. Dollente Mesias & Wei Liu & Jinqing Huang, 2023. "Efficient optical plasmonic tweezer-controlled single-molecule SERS characterization of pH-dependent amylin species in aqueous milieus," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    2. Manjia Li & Byung Min Park & Xin Dai & Yingjie Xu & Jinqing Huang & Fei Sun, 2022. "Controlling synthetic membraneless organelles by a red-light-dependent singlet oxygen-generating protein," Nature Communications, Nature, vol. 13(1), pages 1-13, December.

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