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Small near-infrared photochromic protein for photoacoustic multi-contrast imaging and detection of protein interactions in vivo

Author

Listed:
  • Lei Li

    (California Institute of Technology)

  • Anton A. Shemetov

    (Albert Einstein College of Medicine)

  • Mikhail Baloban

    (Albert Einstein College of Medicine)

  • Peng Hu

    (Washington University in St. Louis)

  • Liren Zhu

    (Washington University in St. Louis
    California Institute of Technology)

  • Daria M. Shcherbakova

    (Albert Einstein College of Medicine)

  • Ruiying Zhang

    (Washington University in St. Louis)

  • Junhui Shi

    (California Institute of Technology)

  • Junjie Yao

    (Duke University)

  • Lihong V. Wang

    (California Institute of Technology
    California Institute of Technology)

  • Vladislav V. Verkhusha

    (Albert Einstein College of Medicine
    University of Helsinki)

Abstract

Photoacoustic (PA) computed tomography (PACT) benefits from genetically encoded probes with photochromic behavior, which dramatically increase detection sensitivity and specificity through photoswitching and differential imaging. Starting with a DrBphP bacterial phytochrome, we have engineered a near-infrared photochromic probe, DrBphP-PCM, which is superior to the full-length RpBphP1 phytochrome previously used in differential PACT. DrBphP-PCM has a smaller size, better folding, and higher photoswitching contrast. We have imaged both DrBphP-PCM and RpBphP1 simultaneously on the basis of their unique signal decay characteristics, using a reversibly switchable single-impulse panoramic PACT (RS-SIP-PACT) with a single wavelength excitation. The simple structural organization of DrBphP-PCM allows engineering a bimolecular PA complementation reporter, a split version of DrBphP-PCM, termed DrSplit. DrSplit enables PA detection of protein–protein interactions in deep-seated mouse tumors and livers, achieving 125-µm spatial resolution and 530-cell sensitivity in vivo. The combination of RS-SIP-PACT with DrBphP-PCM and DrSplit holds great potential for noninvasive multi-contrast deep-tissue functional imaging.

Suggested Citation

  • Lei Li & Anton A. Shemetov & Mikhail Baloban & Peng Hu & Liren Zhu & Daria M. Shcherbakova & Ruiying Zhang & Junhui Shi & Junjie Yao & Lihong V. Wang & Vladislav V. Verkhusha, 2018. "Small near-infrared photochromic protein for photoacoustic multi-contrast imaging and detection of protein interactions in vivo," Nature Communications, Nature, vol. 9(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-05231-3
    DOI: 10.1038/s41467-018-05231-3
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    Cited by:

    1. Ludmila A. Kasatkina & Chenshuo Ma & Mikhail E. Matlashov & Tri Vu & Mucong Li & Andrii A. Kaberniuk & Junjie Yao & Vladislav V. Verkhusha, 2022. "Optogenetic manipulation and photoacoustic imaging using a near-infrared transgenic mouse model," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    2. Xiaoxiang Gao & Xiangjun Chen & Hongjie Hu & Xinyu Wang & Wentong Yue & Jing Mu & Zhiyuan Lou & Ruiqi Zhang & Keren Shi & Xue Chen & Muyang Lin & Baiyan Qi & Sai Zhou & Chengchangfeng Lu & Yue Gu & Xi, 2022. "A photoacoustic patch for three-dimensional imaging of hemoglobin and core temperature," Nature Communications, Nature, vol. 13(1), pages 1-13, December.

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