TY - JOUR
T1 - Small near-infrared photochromic protein for photoacoustic multi-contrast imaging and detection of protein interactions in vivo
AU - Li, Lei
AU - Shemetov, Anton A.
AU - Baloban, Mikhail
AU - Hu, Peng
AU - Zhu, Liren
AU - Shcherbakova, Daria M.
AU - Zhang, Ruiying
AU - Shi, Junhui
AU - Yao, Junjie
AU - Wang, Lihong V.
AU - Verkhusha, Vladislav V.
N1 - Funding Information:
We thank J. Ihalainen (University of Jyväskylä, Finland) for the DrBphP gene and E. Giraud (Institute for Research and Development, France) for the RpBphP1 gene. We also thank P. Zhang and T. Imai for technical support and J. Ballard for technical editing of the manuscript. This work was sponsored by the NIH grants EB016986 (Pioneer Award), CA186567 (Transformative Research Award), NS090579, NS099717, EB016963 (all to L.V.W.), GM122567, NS099573, NS103573, and the EU FP7 grant ERC-2013-ADG-340233 (all to V.V.V.).
PY - 2018/12/1
Y1 - 2018/12/1
N2 - 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.
AB - 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.
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U2 - 10.1038/s41467-018-05231-3
DO - 10.1038/s41467-018-05231-3
M3 - Article
C2 - 30013153
AN - SCOPUS:85050403395
VL - 9
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
IS - 1
M1 - 2734
ER -