AI Chat Paper
Note: Please note that the following content is generated by AMiner AI. SciOpen does not take any responsibility related to this content.
{{lang === 'zh_CN' ? '文章概述' : 'Summary'}}
{{lang === 'en_US' ? '中' : 'Eng'}}
Chat more with AI
Powered by AMiner. Clicking this button will take you away from SciOpen.
Home Nano Research Article
Article Link
Cite
EndNote(RIS) BibTeX
Collect
Submit Manuscript
Show Outline
Outline
Show full outline
Hide outline
Outline
Show full outline
Hide outline
Research Article

Polarity-activated super-resolution imaging probe for the formation and morphology of amyloid fibrils

Zheng Lv1,2,§, Li Li1,§, Zhongwei Man1, Zhenzhen Xu1( ), Hongtu Cui3, Rui Zhan3, Qihua He3, Lemin Zheng3,4 ( ), Hongbing Fu1,2( )
Beijing Key Laboratory for Optical Materials and Photonic Devices, Capital Normal University, Beijing 100048, China
Tianjin Key Laboratory of Molecular Optoelectronic Sciences, Institute of Molecular Plus, Tianjin University, Tianjin 300072, China
The Institute of Cardiovascular Sciences and Institute of Systems Biomedicine, School of Basic Medical Sciences, Key Laboratory of Molecular Cardiovascular Sciences of Ministry of Education, NHC Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Health Science Center, Peking University, Beijing 100191, China
China National Clinical Research Center for Neurological Diseases, Tiantan Hospital, Advanced Innovation Center for Human Brain Protection, The Capital Medical University, Beijing 100050, China

§ Zheng Lv and Li Li contributed equally to this work.

Show Author Information

Graphical Abstract

Abstract

The formation of amyloid plaques usually occurs in the early-stage of Alzheimer’s disease (AD). Stimulated emission depletion (STED) imaging provided a powerful tool for visualizing amyloid structures on the nanometer scale. However, many commercial probes adopted in detecting amyloid fibrils are inapplicable to STED imaging, owing to their unmatched absorption and emission wavelengths, small Stokes’ shift, easy photo-bleaching, etc. Herein, we demonstrated a polarity-activated STED probe based on an intramolecular charge transfer donor (D)-π-acceptor (A) compound. The electron-rich carbazole group and the electron-poor pyridinium bromide group, linked by π-conjugated thiophen-bridge, ensure strong near infrared (NIR) emission with a Stokes’ shift larger than 200 nm. The tiny change in polarity before and after binding with amyloid plaques leads to a transition from weakly emission charge-transfer (CT) state (Φ < 0.04) to highly emissive locally-excited (LE) state (Φ = 0.57), giving rise to a fluorescence Turn-On probe. Together with large Stokes’ shift, good photostability and high depletion efficiency, the super-resolution imaging of the formation and morphology of amyloid fibrils in vitro based on this probe was realized with a lateral spatial resolution better than 33 nm at an extremely low depletion power. Moreover, the ex-vivo super-resolution imaging of (E)-1-butyl-4(2-(5-(9-ethyl-9H-carbazol-3-yl)thiophen-2-yl)vinyl) pyridinium bromide (CTPB) probe in Aβ plaques in the brain slices of a Tg mouse was demonstrated. This research provides a demonstration of the super resolution imaging probe of amyloid fibrils based on polarity-response mechanism, providing a new approach to the development of future amyloid probes.

Keywords

charge transfersuper-resolution imagingamyloid fibrilspolarity-activatednear infrared (NIR) emission

Electronic Supplementary Material

Download File(s)
12274_2020_2899_MOESM1_ESM.pdf (3.1 MB)

References

[1]
Selkoe, D. J. Correction: Corrigendum: Resolving controversies on the path to Alzheimer’s therapeutics. Nat. Med. 2011, 17, 1693.
Crossref Google Scholar
[2]
Masters, C. L.; Simms, G.; Weinman, N. A.; Multhaup, G.; McDonald, B. L.; Beyreuther, K. Amyloid plaque core protein in Alzheimer disease and Down syndrome. Proc. Natl. Acad. Sci. USA 1985, 82, 4245-4249.
Crossref Google Scholar
[3]
Morris, K.; Serpell, L. From natural to designer self-assembling biopolymers, the structural characterisation of fibrous proteins & peptides using fibre diffraction. Chem. Soc. Rev. 2010, 39, 3445-3453.
Crossref Google Scholar
[4]
Hardy, J.; Selkoe, D. J. The amyloid hypothesis of Alzheimer’s disease: Progress and problems on the road to therapeutics. Science 2002, 297, 353-356.
Crossref Google Scholar
[5]
Domike, K. R.; Donald, A. M. Thermal dependence of thermally induced protein spherulite formation and growth: Kinetics of β-lactoglobulin and insulin. Biomacromolecules 2007, 8, 3930-3937.
Crossref Google Scholar
[6]
Rubin, N.; Perugia, E.; Goldschmidt, M.; Fridkin, M.; Addadi, L. Chirality of amyloid suprastructures. J. Am. Chem. Soc. 2008, 130, 4602-4603.
Crossref Google Scholar
[7]
Rodríguez-Rodríguez, C.; Rimola, A.; Rodríguez-Santiago, L.; Ugliengo, P.; Álvarez-Larena, Á.; Gutiérrez-de-Terán, H.; Sodupe, M.; González-Duarte, P. Crystal structure of thioflavin-T and its binding to amyloid fibrils: Insights at the molecular level. Chem. Commun. 2010, 46, 1156-1158.
Crossref Google Scholar
[8]
Yang, Q. L.; Ma, Z. R.; Wang, H. S.; Zhou, B.; Zhu, S. J.; Zhong, Y. T.; Wang, J. Y.; Wan, H.; Antaris, A.; Ma, R. et al. Rational design of molecular fluorophores for biological imaging in the NIR-II window. Adv. Mater. 2017, 29, 1605497.
Crossref Google Scholar
[9]
Mei, J.; Leung, N. L. C.; Kwok, R. T. K.; Lam, J. W. Y.; Tang, B. Z. Aggregation-induced emission: Together we shine, united we soar! Chem. Rev. 2015, 115, 11718-11940.
Crossref Google Scholar
[10]
Guo, Z. Q.; Park, S.; Yoon, J.; Shin, I. Recent progress in the development of near-infrared fluorescent probes for bioimaging applications. Chem. Soc. Rev. 2014, 43, 16-29.
Crossref Google Scholar
[11]
Wang, Y. L.; Fan, C.; Xin, B.; Zhang, J. P.; Luo, T.; Chen, Z. Q.; Zhou, Q. Y.; Yu, Q.; Li, X. N.; Huang, Z. L. et al. AIE-based super-resolution imaging probes for β-amyloid plaques in mouse brains. Mater. Chem. Front. 2018, 2, 1554-1562.
Crossref Google Scholar
[12]
Li, D. Y.; Qin, W.; Xu, B.; Qian, J.; Tang, B. Z. AIE nanoparticles with high stimulated emission depletion efficiency and photobleaching resistance for long-term super-resolution bioimaging. Adv. Mater. 2017, 29, 1703643.
Crossref Google Scholar
[13]
Liu, Y. J.; Lu, Y. Q.; Yang, X. S.; Zheng, X. L.; Wen, S. H.; Wang, F.; Vidal, X.; Zhao, J. B.; Liu, D. M.; Zhou, Z. G. et al. Amplified stimulated emission in upconversion nanoparticles for super-resolution nanoscopy. Nature 2017, 543, 229-233.
Crossref Google Scholar
[14]
Vicidomini, G.; Bianchini, P.; Diaspro, A. STED super-resolved microscopy. Nat. Methods 2018, 15, 173-182.
Crossref Google Scholar
[15]
Wang, L.; Frei, M. S.; Salim, A.; Johnsson, K. Small-molecule fluorescent probes for live-cell super-resolution microscopy. J. Am. Chem. Soc. 2019, 141, 2770-2781.
Crossref Google Scholar
[16]
Zhang, T.; Li, S. P.; Du, Y.; He, T.; Shen, Y. B.; Bai, C.; Huang, Y. J.; Zhou, X. C. Revealing the activity distribution of a single nanocatalyst by locating single nanobubbles with super-resolution microscopy. J. Phys. Chem. Lett. 2018, 9, 5630-5635.
Crossref Google Scholar
[17]
Wang, H. H.; Zhang, T.; Zhou, X. C. Dark-field spectroscopy: Development, applications and perspectives in single nanoparticle catalysis. J. Phys. Condens. Matter 2019, 31, 473001.
Crossref Google Scholar
[18]
Groenning, M. Binding mode of Thioflavin T and other molecular probes in the context of amyloid fibrils-current status. J. Chem. Biol. 2010, 3, 1-18.
Crossref Google Scholar
[19]
Younan, N. D.; Viles, J. H. A comparison of three fluorophores for the detection of amyloid fibers and prefibrillar oligomeric assemblies. ThT (Thioflavin T); ANS (1-anilinonaphthalene-8-sulfonic acid); and bisANS (4,4’-dianilino-1,1’-binaphthyl-5,5’-disulfonic acid). Biochemistry 2015, 54, 4297-4306.
Crossref Google Scholar
[20]
Hintersteiner, M.; Enz, A.; Frey, P.; Jaton, A. L.; Kinzy, W.; Kneuer, R.; Neumann, U.; Rudin, M.; Staufenbiel, M.; Stoeckli, M. et al. In vivo detection of amyloid-β deposits by near-infrared imaging using an oxazine-derivative probe. Nat. Biotechnol. 2005, 23, 577-583.
Crossref Google Scholar
[21]
Hsu, J. C. C.; Chen, E. H. L.; Snoeberger, R. C.; Luh, F. Y.; Lim, T. S.; Hsu, C. P.; Chen, R. P. Y. Thioflavin T and its photoirradiative derivatives: Exploring their spectroscopic properties in the absence and presence of amyloid fibrils. J. Phys. Chem. B 2013, 117, 3459-3468.
Crossref Google Scholar
[22]
Qi, J.; Sun, C. W.; Zebibula, A.; Zhang, H. Q.; Kwok, R. T. K.; Zhao, X. Y.; Xi, W.; Lam, J. W. Y.; Qian, J.; Tang, B. Z. Real-time and high-resolution bioimaging with bright aggregation-induced emission dots in short-wave infrared region. Adv. Mater. 2018, 30, 1706856.
Crossref Google Scholar
[23]
Zhang, W.; Wen, Y.; He, D. X.; Wang, Y. F.; Liu, X. L.; Li, C.; Liang, X. J. Near-infrared AIEgens as transformers to enhance tumor treatment efficacy with controllable self-assembled redox-responsive carrier-free nanodrug. Biomaterials 2019, 193, 12-21.
Crossref Google Scholar
[24]
Fu, W.; Yan, C. X.; Guo, Z. Q.; Zhang, J. J.; Zhang, H. Y.; Tian, H.; Zhu, W. H. Rational design of near-infrared aggregation-induced-emission-active probes: In situ mapping of amyloid-β plaques with ultrasensitivity and high-fidelity. J. Am. Chem. Soc. 2019, 141, 3171-3177.
Crossref Google Scholar
[25]
Xu, Y. Z.; Zhang, H. K.; Zhang, N.; Wang, X. C.; Dang, D. F.; Jing, X. N.; Xi, D.; Hao, Y.; Tang, B. Z.; Meng, L. J. Deep-red fluorescent organic nanoparticles with high brightness and photostability for super-resolution in vitro and in vivo imaging using STED nanoscopy. ACS Appl. Mater. Interfaces 2020, 12, 6814-6826.
Crossref Google Scholar
[26]
Jiang, N.; Fan, J. L.; Xu, F.; Peng, X. J.; Mu, H. Y.; Wang, J. Y.; Xiong, X. Q. Ratiometric fluorescence imaging of cellular polarity: Decrease in mitochondrial polarity in cancer cells. Angew. Chem., Int. Ed. 2015, 54, 2510-2514.
Crossref Google Scholar
[27]
Powers, E. T.; Morimoto, R. I.; Dillin, A.; Kelly, J. W.; Balch, W. E. Biological and chemical approaches to diseases of proteostasis deficiency. Annu. Rev. Biochem. 2009, 78, 959-991.
Crossref Google Scholar
[28]
Suppan, P. Solvent effects on energy of electronic transitions-experimental observations and applications to structural problems of excited molecules. J. Chem. Soc. A. Inorg. Phys. Theor. 1968, 3125-3133.
Crossref Google Scholar
[29]
Szczupak, B.; Ryder, A. G.; Togashi, D. M.; Klymchenko, A. S.; Rochev, Y. A.; Gorelov, A.; Glynn, T. J. Polarity assessment of thermoresponsive poly(NIPAM-co-NtBA) copolymer films using fluorescence methods. J. Fluoresc. 2010, 20, 719-731.
Crossref Google Scholar
[30]
Heo, C. H.; Sarkar, A. R.; Baik, S. H.; Jung, T. S.; Kim, J. J.; Kang, H.; Mook-Jung, I.; Kim, H. M. A quadrupolar two-photon fluorescent probe for in vivo imaging of amyloid-β plaques. Chem. Sci. 2016, 7, 4600-4606.
Crossref Google Scholar
[31]
Mishra, R.; Sjölander, D.; Hammarström, P. Spectroscopic characterization of diverse amyloid fibrils in vitro by the fluorescent dyeNile red. Mol. Biosyst. 2011, 7, 1232-1240.
Crossref Google Scholar
[32]
Sackett, D. L.; Wolff, J. Nile red as a polarity-sensitive fluorescent probe of hydrophobic protein surfaces. Anal. Biochem. 1987, 167, 228-234.
Crossref Google Scholar
[33]
Sharonov, A.; Hochstrasser, R. M. Wide-field subdiffraction imaging by accumulated binding of diffusing probes. Proc. Natl. Acad. Sci. USA 2006, 103, 18911-18916.
Crossref Google Scholar
[34]
Zhou, K. X.; Yuan, C.; Dai, B.; Wang, K.; Chen, Y. M.; Ma, D. L.; Dai, J. P.; Liang, Y.; Tan, H. W.; Cui, M. C. Environment-sensitive near-infrared probe for fluorescent discrimination of aβ and tau fibrils in AD brain. J. Med. Chem. 2019, 62, 6694-6704.
Crossref Google Scholar
[35]
Lee, J. E.; Sang, J. C.; Rodrigues, M.; Carr, A. R.; Horrocks, M. H.; De, S. M.; Bongiovanni, M. N.; Flagmeier, P.; Dobson, C. M.; Wales, D. J. et al. Mapping surface hydrophobicity of α-synuclein oligomers at the nanoscale. Nano Lett. 2018, 18, 7494-7501.
Crossref Google Scholar
[36]
Grabowski, Z. R.; Rotkiewicz, K.; Rettig, W. Structural changes accompanying intramolecular electron transfer: Focus on twisted intramolecular charge-transfer states and structures. Chem. Rev. 2003, 103, 3899-4032.
Crossref Google Scholar
[37]
Hong, Y. N.; Meng, L. M.; Chen, S. J.; Leung, C. W. T.; Da, L. T.; Faisal, M.; Silva, D. A.; Liu, J. Z.; Lam, J. W. Y.; Huang, X. H. et al. Monitoring and inhibition of insulin fibrillation by a small organic fluorogen with aggregation-induced emission characteristics. J. Am. Chem. Soc. 2012, 134, 1680-1689.
Crossref Google Scholar
[38]
Spehar, K.; Ding, T. B.; Sun, Y. Z.; Kedia, N.; Lu, J.; Nahass, G. R.; Lew, M. D.; Bieschke, J. Super-resolution imaging of amyloid structures over extended times by using transient binding of single thioflavin t molecules. Chembiochem 2018, 19, 1944-1948.
Crossref Google Scholar
[39]
Biancalana, M.; Koide, S. Molecular mechanism of Thioflavin-T binding to amyloid fibrils. Biochim. Biophys. Acta 2010, 1804, 1405-1412.
Crossref Google Scholar
[40]
Batzli, K. M.; Love, B. J. Agitation of amyloid proteins to speed aggregation measured by ThT fluorescence: A call for standardization. Mater. Sci. Eng. C 2015, 48, 359-364.
Crossref Google Scholar
[41]
Greenwald, J.; Riek, R. Biology of amyloid: Structure, function, and regulation. Structure 2010, 18, 1244-1260.
Crossref Google Scholar
[42]
Guo, S. L.; Akhremitchev, B. B. Packing density and structural heterogeneity of insulin amyloid fibrils measured by AFM nanoindentation. Biomacromolecules 2006, 7, 1630-1636.
Crossref Google Scholar
[43]
Koffie, R. M.; Meyer-Luehmann, M.; Hashimoto, T.; Adams, K. W.; Mielke, M. L.; Garcia-Alloza, M.; Micheva, K. D.; Smith, S. J.; Kim, M. L.; Lee, V. M. et al. Oligomeric amyloid β associates with postsynaptic densities and correlates with excitatory synapse loss near senile plaques. Proc. Natl. Acad. Sci. USA 2009, 106, 4012-4017.
Crossref Google Scholar
[44]
Varongchayakul, N.; Johnson, S.; Quabili, T.; Cappello, J.; Ghandehari, H.; de Jesus Solares, S.; Hwang, W.; Seog, J. Direct observation of amyloid nucleation under nanomechanical stretching. ACS Nano 2013, 7, 7734-7743.
Crossref Google Scholar
[45]
Ries, J.; Udayar, V.; Soragni, A.; Hornemann, S.; Nilsson, K. P. R.; Riek, R.; Hock, C.; Ewers, H.; Aguzzi, A. A.; Rajendran, L. Superresolution imaging of amyloid fibrils with binding-activated probes. ACS Chem. Neurosci. 2013, 4, 1057-1061.
Crossref Google Scholar
[46]
Kaminski Schierle, G. S.; van de Linde, S.; Erdelyi, M.; Esbjörner, E. K.; Klein, T.; Rees, E.; Bertoncini, C. W.; Dobson, C. M.; Sauer, M.; Kaminski, C. F. In situ measurements of the formation and morphology of intracellular β-amyloid fibrils by super-resolution fluorescence imaging. J. Am. Chem. Soc. 2011, 133, 12902-12905.
Crossref Google Scholar
[47]
Cui, M. C.; Ono, M.; Watanabe, H.; Kimura, H.; Liu, B.; Saji, H. Smart near-infrared fluorescence probes with donor-acceptor structure for in vivo detection of β-amyloid deposits. J. Am. Chem. Soc. 2014, 136, 3388-3394.
Crossref Google Scholar
Nano Research
Volume 13 Issue 9,
September 2020
Pages 2556-2563
DOI: 10.1007/s12274-020-2899-1
Cite this article:
Lv Z, Li L, Man Z, et al. Polarity-activated super-resolution imaging probe for the formation and morphology of amyloid fibrils. Nano Research, 2020, 13(9): 2556-2563. https://doi.org/10.1007/s12274-020-2899-1
Topics:
Infrared devices MorphologyProbes

753

Views

13

Crossref

N/A

Web of Science

12

Scopus

0

CSCD

Altmetrics
Received: 26 March 2020
Revised: 21 May 2020
Accepted: 22 May 2020
Published: 25 June 2020
© Tsinghua University Press and Springer-Verlag GmbH Germany, part of Springer Nature 2020
Return