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

Lei Li, Anton A. Shemetov, Mikhail Baloban, Peng Hu, Liren Zhu, Daria M. Shcherbakova, Ruiying Zhang, Junhui Shi, Junjie Yao, Lihong V. Wang () and Vladislav V. Verkhusha ()
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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
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
Vladislav V. Verkhusha: Albert Einstein College of Medicine

Nature Communications, 2018, vol. 9, issue 1, 1-14

Abstract: 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.

Date: 2018
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DOI: 10.1038/s41467-018-05231-3

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