Review

Visualization Imaging of Cell Membrane Receptor Proteins Based on Non-genetic Engineering Approaches

  • Miaomiao Zhou ,
  • Haowen Cao ,
  • Xinyi Yang ,
  • Xinyi Ren ,
  • Feng Yao ,
  • Leiliang He
Expand
  • a College of Public Health, Zhengzhou University, Zhengzhou 450001, China
    b Nanchang Disease Prevention and Control Institute, China Railway Nanchang Bureau Group Co., Ltd., Nanchang 330003, China

Received date: 2024-12-03

  Online published: 2025-01-24

Supported by

National Natural Science Foundations of China(82373630); National Natural Science Foundations of China(82073606); training grant of Henan Province for Young Backbone Teachers(2023GGJS009)

Abstract

Cell membrane receptor proteins are important mediators for communication between cells and the external environment. Changes in their expression levels or behavior may indicate the initiation of certain physiological or pathological processes in the body, and many cell membrane receptor proteins have been used as a basis for identifying different cell populations or subtypes and as targets for targeted therapy. Traditional genetic engineering protein imaging strategies involve genetic manipulation, which may interfere with other biological processes within the cell and have unpredictable limitations. Therefore, non-genetic engineering protein imaging strategies have gained significant attention in tumor visualization imaging research, mainly due to their notable characteristics, including simplicity, programmable design, and ease of regulation, and have been widely used in the imaging studies of cell membrane receptor proteins. This review comprehensively summarizes the use of non-genetic engineering strategies for cell membrane receptor protein imaging. It includes the design of logical gate probes, fluorescence resonance energy transfer (FRET) probes, structurally constrained hybridization probes, and signal tags for cell type identification; secondly, it summarizes the application of this protein imaging mode in the interaction of cell membrane receptor proteins, where receptor dimerization in the interaction of membrane receptor proteins is the first step in receptor activation and cell communication, and the visualization of membrane receptor dimerization is achieved by designing DNA probe systems and fluorescent sensors. Additionally, this review covers the application of spatial distribution analysis imaging of cell membrane receptor proteins, achieving nanometer-level spatial distribution imaging of membrane receptors through single-molecule localization microscopy (SMLM) and point accumulation for imaging in nanoscale topography (PAINT); finally, it looks forward to the challenges faced in this field and future development directions. With advancements in DNA nanotechnology, imaging technology, and bioinformatics, future research on non-genetic engineering strategies could provide higher resolution and more in-depth imaging of cell membrane receptor proteins, thereby offering more innovative pathways for in-depth study of intercellular communication mechanisms.

Cite this article

Miaomiao Zhou , Haowen Cao , Xinyi Yang , Xinyi Ren , Feng Yao , Leiliang He . Visualization Imaging of Cell Membrane Receptor Proteins Based on Non-genetic Engineering Approaches[J]. Acta Chimica Sinica, 2025 , 83(3) : 299 -308 . DOI: 10.6023/A24120363

References

[1]
Chen, J.-B.; Chou, F.-J.; Yeh, S.-Y.; Ou, Z.-Y.; Shyr, C.; Huang, C.-P.; Xiang, Z.-D.; Sun, Y.; Messing, E.; Zu, X.-B.; Chang, C. Oncogene 2020, 39, 574.
[2]
Pedram, A.; Razandi, M.; Lewis, M.; Hammes, S.; Levin, E. R. Dev. Cell 2014, 29, 482.
[3]
Dong, M.-D.; Zhang, H.; Mo, C.-Y.; Li, W.-J.; Zhang, W.-W.; Jia, K.-T.; Liu, W.; Yi, M.-S. Int. J. Mol. Sci. 2021, 22, 10022.
[4]
Sanganna-Gari, R. R.; Montalvo-Acosta, J. J.; Heath, G. R.; Jiang, Y. N.; Gao, X. L.; Nimigean, C. M.; Chipot, C.; Scheuring, S. Nat. Commun. 2021, 12, 4363.
[5]
Itakura, M.; Yamaguchi, K.; Kitazawa, R.; Lim, S. Y.; Anan, Y.; Yoshitake, J.; Shibata, T.; Negishi, L.; Sugawa, H.; Nagai, R.; Uchida, K. Nat. Commun. 2022, 13, 2974.
[6]
Yu, L.-M.; Di, W.-C.; Dong, X.; Li, Z.; Zhang, Y.; Xue, X.-D.; Xu, Y.-L.; Zhang, J.; Xiao, X.; Han, J.-S.; Liu, Y.; Yang, Y.; Wang, H.-S. Biochim. Biophys. Acta Mol. Basis Dis. 2018, 1864, 563.
[7]
Brown, D. M.; Ruoslahti, E. Cancer Cell 2004, 5, 365.
[8]
Liu, Y.; Wang, W.-L.; Zhao, Q.; Yuan, P.; Li, J.-X.; Song, X.-R.; Liu, Z.-Q.; Ding, D.-W.; Wang, L.-L.; Song, L.-S. Dev. Comp. Immunol. 2021, 116, 103937.
[9]
Rowland, R.; Brandariz-Nu?ez, A. Microbiol. Spectr. 2021, 9, e0119921.
[10]
Kuhlmann, L.; Govindarajan, M.; Mejia-Guerrero, S.; Ignatchenko, V.; Liu, L.-Y.; Grünwald, B. T.; Cruickshank, J.; Berman, H.; Khokha, R.; Kislinger, T. J. Proteome Res. 2022, 21, 2224.
[11]
Kim, K. M.; Noh, J. H.; Bodogai, M.; Martindale, J. L.; Yang, X.; Indig, F. E.; Basu, S. K.; Ohnuma, K.; Morimoto, C.; Johnson, P. F.; Biragyn, A.; Abdelmohsen, K.; Gorospe, M. Genes Dev. 2017, 31, 1529.
[12]
Wang, B.; Cai, X.-D.; Xiao, J.-X. Acta Chim. Sinica 2024, 82, 367 (in Chinese).
[12]
(王博, 蔡向东, 肖建喜, 化学学报, 2024, 82, 367.)
[13]
Cai, Z.-M.; Xie, C.-H.; Qiao, W.; Fei, X.-B.; Guo, X.-X.; Liu, H.-C.; Li, X.-Y.; Fang, X.; Xu, G.-Q.; Dou, H.; Deng, G.-M. Front. Immunol. 2017, 8, 1723.
[14]
Huisman, W.; Gille, I.; VanderMaarel, L. E.; Hageman, L.; Morton, L. T.; de Jong, R. C. M.; Heemskerk, M. H. M.; Amsen, D.; Falkenburg, J. H. F.; Jedema, I. J. Infect. Dis. 2022, 226, 833.
[15]
Zhang, P.-S.; Jing, L.-H. Acta Chim. Sinica 2022, 80, 805 (in Chinese).
[15]
(张沛森, 荆莉红, 化学学报, 2022, 80, 805.).
[16]
Babelova, L.; Sohova, M. E.; Poturnayova, A.; Buríková, M.; Bizík, J.; Hianik, T. Electroanalysis 2018, 30, 1487.
[17]
Huang, Y.-Q.; Luo, J.-W.; Li, J.-Q.; Zhang, R.; Liu, X.-F.; Fan, Q.-L.; Huang, W. Acta Chim. Sinica 2024, 82, 903 (in Chinese).
[17]
(黄艳琴, 罗集文, 李佳启, 张瑞, 刘兴奋, 范曲立, 黄维, 化学学报, 2024, 82, 903.)
[18]
Kanayasu-Toyoda, T.; Tanaka, T.; Kikuchi, Y.; Uchida, E.; Matsuyama, A.; Yamaguchi, T. J. Stem Cells 2016, 34, 1251.
[19]
Tran, H. T. T.; Gigl, M.; Le, N. P. K.; Dawid, C.; Lamy, E. J. Pharmaceuticals (Basel) 2021, 14, 1055.
[20]
Tilli, T. M. J. Pers. Med. 2021, 11, 1348.
[21]
Rusinova, R.; He, C.; Andersen, O. S. Proc. Natl. Acad. Sci. U. S. A. 2021, 118, e2113229118.
[22]
Remington, S. Protein Sci. 2011, 20, 1509.
[23]
Kong, J.; Wang, Y.-F.; Qi, W.; Huang, M.-M.; Su, R.-X.; He, Z. M. Adv. Colloid Interface Sci. 2020, 285, 102286.
[24]
VanThor, J. J.; Champion, P. M. Annu. Rev. Phys. Chem. 2023, 74, 123.
[25]
Liang, G.-T.; Lai, C.-X.; Yue, Z.-J.; Zhang, H.-B.; Li, D.-Y.; Chen, Z.; Lu, X.-Y.; Tao, L.; Subach, F. V.; Piatkevich, K. D. Front. Bioeng. Biotechnol. 2022, 10, 1039317.
[26]
Zhang, S.; Ai, H.-W. Nat. Chem. Biol. 2020, 16, 1434.
[27]
Hirano, M.; Ando, R.; Shimozono, S.; Sugiyama, M.; Takeda, N.; Kurokawa, H.; Deguchi, R.; Endo, K.; Haga, K.; Takai-Todaka, R.; Inaura, S.; Matsumura, Y.; Hama, H.; Okada, Y.; Fujiwara, T.; Morimoto, T.; Katayama, K.; Miyawaki, A. Nat. Biotechnol. 2022, 40, 1132.
[28]
Qu, Z.; Fang, J.; Wang, Y.-X.; Sun, Y.; Liu, Y.; Wu, W.-H.; Zhang, W.-B. Nat. Commun. 2023, 14, 3480.
[29]
Pedelacq, J. D.; Cabantous, S. Int. J. Mol. Sci. 2019, 20, 3479.
[30]
You, M.; Peng, L.; Shao, N.; Zhang, L.; Qiu, L.; Cui, C.; Tan, W. J. Am. Chem. Soc. 2014, 136, 1256.
[31]
Douglas, S. M.; Bachelet, I.; Church, G. M. Science 2012, 335, 831.
[32]
Chang, X.; Zhang, C.; Lv, C.; Sun, Y.; Zhang, M.; Zhao, Y.; Yang, L.; Han, D.; Tan, W. J. Am. Chem. Soc. 2019, 141, 12738.
[33]
Peng, R.; Zheng, X.; Lyu, Y.; Xu, L.; Zhang, X.; Ke, G.; Liu, Q.; You, C.; Huan, S.; Tan, W. J. Am. Chem. Soc. 2018, 140, 9793.
[34]
Feng, C.; Chen, T.; Mao, D.; Zhang, F.; Tian, B.; Zhu, X. ACS Sens. 2020, 5, 3116.
[35]
Yuan, K.; Meng, H.-M.; Wu, Y.-A. CCS Chem. 2022, 4, 1597.
[36]
Chen, B.; Ma, W.; Long, X.; Cheng, H.; Sun, H.; Huang, J.; Jia, R. He, X.; Wang, K. Anal. Chem. 2022, 94, 2502.
[37]
Li, Y.; Zhang, X.; Pan, W.; Li, N.; Tang, B. Anal. Chem. 2020, 92, 11921.
[38]
Ang, Y. S.; Li, J. J.; Chua, P. J.; Ng, C. T.; Bay, B. H.; Yung, L. L. Anal. Chem. 2018, 90, 6193.
[39]
Wu, N.; Bao, L.; Ding, L.; Ju, H. Angew. Chem. Int. Ed. 2016, 55, 5220.
[40]
Yuan, B.; Chen, Y.; Sun, Y.; Guo, Q; Huang, J.; Liu, J.; Meng, X.; Yang, X.; Wen, X.; Li, Z.; Li, L.; Wang, K. Anal. Chem. 2018, 90, 6131.
[41]
Li, N.; Zhang, W.; Lin, L.; Shah, S. N. A.; Li, Y.; Lin, J.-M. Anal. Chem. 2019, 91, 2600.
[42]
Zhu, L.; Xu, Y.; Wei, X.; Lin, H.; Huang, M.; Lin, B.; Song, Y.; Yang, C. Angew. Chem. Int. Ed. 2021, 60, 18111.
[43]
Huang, M.; Zhu, L.; Kang, S.; Chen, F.; Wei, X.; Lin, L.; Chen, X.; Wang, W.; Zhu, Z.; Yang, C.; Song, Y. Anal. Chem. 2021, 93, 15958.
[44]
Ang, Y. S.; Yung, L. L. Nucleic Acids Res. 2021, 49, 4258.
[45]
Huang, F.; You, M.; Han, D.; Xiong, X.; Liang, H.; Tan, W. J. Am. Chem. Soc. 2013, 135, 7967.
[46]
Idili, A.; Porchetta, A.; Amodio, A.; Vallée-Bélisle, A.; Ricci, F. Nano Lett. 2015, 15, 5539.
[47]
Shi, H.; Lei, Y.; Ge, J.; He, X.; Cui, W.; Ye, X.; Liu, J.; Wang, K. Anal. Chem. 2019, 91, 9154.
[48]
Yang, T.; Xu, L.; Liu, S.; Shen, Y.; Huang, L.; Zhang, L.; Ding, S.; Cheng, W. Mikrochim. Acta 2019, 186, 439.
[49]
Liu, L.; Li, S.; Mao, A.; Wang, G.; Liu, Y.; Ju, H.; Ding, L. Chem. Sci. 2020, 11, 1665.
[50]
Liu, Z.; Liang, Y.; Cao, W.; Gao, W.; Tang, B. Anal. Chem. 2021, 93, 8915.
[51]
Lei, Y.; Tang, J.; Shi, H.; Ye, X.; He, X.; Xu, F.; Yan, L.; Qiao, Z.; Wang, K. Anal. Chem. 2016, 88, 11699.
[52]
G?tzke, H.; Kilisch, M.; Martínez-Carranza, M.; Sograte-Idrissi, S.; Rajavel, A.; Schlichthaerle, T.; Engels, N.; Jungmann, R.; Stenmark, P.; Opazo, F.; Frey, S. Nat. Commun. 2019, 10, 4403.
[53]
Sato, R.; Kozuka, J.; Ueda, M.; Mishima, R.; Kumagai, Y.; Yoshimura, A.; Minoshima, M.; Mizukami, S.; Kikuchi, K. J. Am. Chem. Soc. 2017, 139, 17397.
[54]
Hayashi, T.; Hamachi, I. Acc. Chem. Res. 2012, 45, 1460.
[55]
Karch, S.; Broichhagen, J.; Schneider, J.; B?ning, D.; Hartmann, S.; Schmid, B.; Tripal, P.; Palmisano, R.; Alzheimer, C.; Johnsson, K.; Huth, T. J. Med. Chem. 2018, 61, 6121.
[56]
Zhuang, H.; Matsunami, H. Nat. Protoc. 2008, 3, 1402.
[57]
Jensen, E. C. Anat. Rec. (Hoboken) 2012, 295, 2031.
[58]
Lang, K.; Chin, J.-W. Chem. Rev. 2014, 114, 4764.
[59]
George, N.; Pick, H.; Vogel, H.; Johnsson, N.; Johnsson, K. J. Am. Chem. Soc. 2004, 126, 8896.
[60]
Miller, L. W.; Cai, Y.; Sheetz, M. P.; Cornish, V. W. Nat. Methods 2005, 2, 255.
[61]
Popp, M. W.; Antos, J. M.; Grotenbreg, G. M.; Spooner, E.; Ploegh, H. L. Nat. Chem. Biol. 2007, 3, 707.
[62]
Poc, P.; Gutzeit, V. A.; Ast, J.; Lee, J.; Jones, B. J.; D'Este, E.; Mathes, B.; Lehmann, M.; Hodson, D. J.; Levitz, J.; Broichhagen, J. Chem. Sci. 2020, 11, 7871.
[63]
Birke, R.; Ast, J.; Roosen, D. A.; Lee, J.; Ro?mann, K.; Huhn, C.; Mathes, B.; Lisurek, M.; Bushiri, D.; Sun, H.; Jones, B.; Lehmann, M.; Levitz, J.; Haucke, V.; Hodson, D. J.; Broichhagen, J. Org. Biomol. Chem. 2022, 20, 5967.
[64]
Liu, Q.; Zheng, J.; Sun, W.; Huo, Y.; Zhang, L.; Hao, P.; Wang, H.; Zhuang, M. Nat. Methods 2018, 15, 715.
[65]
Wang, Y.; Zhang, N.; Lu, S.; Wang, J.; Bing, T.; Liu, X.; Chen, C.; Shang, G.-D. Anal. Chem. 2019, 91, 13720.
[66]
Liu, L.; Kuang, Y.; Wang, Z.; Chen, Y. Chem. Sci. 2020, 11, 11298.
[67]
Zhang, X.; Yin, J.; Pan, W.; Li, Y.; Li, N.; Tang, B. Anal. Bioanal. Chem. 2022, 67, 82.
[68]
Lemmon, M. A.; Schlessinger, J. Cell 2010, 141, 1117.
[69]
Pellat, A.; Vaquero, J.; Fouassier, L. J. Hepatology 2018, 67, 762.
[70]
Leippe, P.; Broichhagen, J.; Cailliau, K.; Mougel, A.; Morel, M.; Dissous, C.; Trauner, D.; Vicogne, J. Angew. Chem. Int. Ed. 2020, 59, 6720.
[71]
Trenker, R.; Jura, N. Curr. Opin. Cell Biol. 2020, 63, 174.
[72]
Brizzolara, A.; Benelli, R.; Venè, R.; Barboro, P.; Poggi, A.; Tosetti, F.; Ferrari, N. Cancer Lett. 2017, 400, 9.
[73]
Song, D.; Jung, Y. Angew. Chem. Int. Ed. 2019, 58, 2045.
[74]
Coban, O.; Zanetti-Dominguez, L. C.; Matthews, D. R.; Rolfe, D. J.; Weitsman, G.; Barber, P. R.; Barbeau, J.; Devauges, V.; Kampmeier, F.; Winn, M.; Vojnovic, B.; Parker, P. J.; Lidke, K. A.; Lidke, D. S.; Ameer-Beg, S. M.; Martin-Fernandez, M. L.; Ng, T. Biophys. J. 2015, 108, 1013.
[75]
Liang, H.; Chen, S.; Li, P.; Wang, L.; Li, J.; Li, J.; Yang, H. H.; Tan, W. J. Am. Chem. Soc. 2018, 140, 4186.
[76]
Wang, L.; Li, W.; Sun, J.; Zhang, S. Y.; Yang, S.; Li, J.; Li, J.; Yang, H. H. Anal. Chem. 2018, 90, 14433.
[77]
Kan, A.-L.; Ding, S.-Y.; Zhang, N.; Jiang, W. Sensors and Actuators B-Chemical 2022, 350, 0925.
[78]
Yin, J.; Jiao, Y.; Peng, X.; He, H.; Duan, C. Biosens. Bioelectron. 2020, 153, 112026.
[79]
Jiao, Y.; Yin, J.; He, H.; Peng, X.; Gao, Q.; Duan, C. J. Am. Chem. Soc. 2018, 140, 5882.
[80]
Torelli, M. D.; Rickard, A. G.; Backer, M. V.; Filonov, D. S.; Nunn, N. A.; Kinev, A. V.; Backer, J. M.; Palmer, G. M.; Shenderova, O. A. Bioconjug. Chem. 2019, 30, 604.
[81]
Stone, M. B.; Shelby, S. A.; Veatch, S. L. Chem. Rev. 2017, 117, 7457.
[82]
Sauer, M.; Heilemann, M. Chem. Rev. 2017, 117, 7478.
[83]
Yang, W.; Nan, H.; Xu, Z.; Huang, Z.; Chen, S.; Li, J.; Li, J.; Yang, H. Anal. Chem. 2021, 93, 12265.
[84]
Manzo, C.; Garcia-Parajo, M. F. Rep. Prog. Phys. 2015, 78, 124601.
[85]
Marchetti, L.; Bonsignore, F.; Gobbo, F.; Amodeo, R.; Calvello, M.; Jacob, A.; Signore, G.; Schirripa Spagnolo, C.; Porciani, D.; Mainardi, M.; Beltram, F.; Luin, S.; Cattaneo, A. Proc. Natl. Acad. Sci. U. S. A. 2019, 116, 21563.
[86]
Delcanale, P.; Porciani, D.; Pujals, S.; Jurkevich, A.; Chetrusca, A.; Tawiah, K. D.; Burke, D. H.; Albertazzi, L. Angew. Chem. Int. Ed. 2020, 59, 18546.
[87]
Winckler, P.; Lartigue, L.; Giannone, G.; DeGiorgi, F.; Ichas, F.; Sibarita, J. B.; Lounis, B.; Cognet, L. Sci. Rep. 2013, 3, 2387.
[88]
Clowsley, A. H.; Kaufhold, W. T.; Lutz, T.; Meletiou, A.; Di Michele, L.; Soeller, C. J. Am. Chem. Soc. 2020, 142, 12069.
[89]
Chien, F. C.; Lin, C.-Y.; Abrigo, G. Anal. Chem. 2021, 93, 15401.
Outlines

/