Skip to main content

Expansion Microscopy for Brain Imaging

  • Chapter
  • First Online:
Advanced Optical Methods for Brain Imaging

Part of the book series: Progress in Optical Science and Photonics ((POSP,volume 5))

  • 1734 Accesses

Abstract

Understanding the organ-wide molecular architecture of proteins is required to dissect the mechanisms of various diseases and answer many scientific questions. Accordingly, there is a significant need for an imaging methodology that is capable of imaging proteins at nanoscale resolution over whole organs. In 2015, a technique called expansion microscopy (ExM) was developed. This technique increases the resolution of conventional microscopy several-fold by physically expanding a specimen with a swellable polymer network. After expansion, specimens become transparent, enabling super-resolution imaging of relatively thick tissue slices without ultra-thin sectioning. Recently, multiple ExM variants which demonstrated expansion microscopy with conventional fluorophore-conjugated antibodies, super-resolution imaging of RNA in cells and tissue slices via expansion, multiplexed protein imaging via post-expansion antibody staining, and sub-20-nm resolution via expanding specimens more than 20-fold have been developed. This chapter presents the detailed molecular principles of ExM and its variants to understand the differences between various ExM-related techniques.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. M.J. Rust, M. Bates, X. Zhuang, Sub-diffraction-limit imaging by stochastic optical reconstruction microscopy (STORM). Nat. Methods 3, 793 (2006)

    Article  Google Scholar 

  2. G.T. Dempsey, J.C. Vaughan, K.H. Chen, M. Bates, X. Zhuang, Evaluation of fluorophores for optimal performance in localization-based super-resolution imaging. Nat. Methods 8, 1027–1036 (2011)

    Article  Google Scholar 

  3. J.C. Vaughan, S. Jia, X. Zhuang, Ultrabright photoactivatable fluorophores created by reductive caging. Nat. Methods 9, 1181–1184 (2012)

    Article  Google Scholar 

  4. N. Olivier, D. Keller, P. Gönczy, S. Manley, Resolution doubling in 3D-STORM imaging through improved buffers. PLoS ONE 8, e69004 (2013)

    Article  Google Scholar 

  5. P. Engerer, C. Fecher, T. Misgeld, Super-resolution microscopy writ large. Nat. Biotechnol. 34, 928 (2016)

    Article  Google Scholar 

  6. F. Chen, P. Tillberg, E.S. Boyden, Expansion microscopy. Science (80) 347, 543 (2015)

    Article  Google Scholar 

  7. F. Chen et al., Nanoscale imaging of RNA with expansion microscopy. Nat. Methods 13, 679–684 (2016)

    Article  Google Scholar 

  8. J.-B. Chang et al., Iterative expansion microscopy. Nat. Methods 14, 593–599 (2017)

    Article  Google Scholar 

  9. P.W. Tillberg et al., Protein-retention expansion microscopy of cells and tissues labeled using standard fluorescent proteins and antibodies. Nat. Biotechnol. 34, 987–992 (2016)

    Article  Google Scholar 

  10. H. Cang, et al., Ex-STORM: expansion single molecule nanoscopy. bioRxiv (2016)

    Google Scholar 

  11. Y.S. Zhang et al., Hybrid microscopy: enabling inexpensive high-performance imaging through combined physical and optical magnifications. Sci. Rep. 6, 22691 (2016)

    Article  Google Scholar 

  12. T.J. Chozinski et al., Expansion microscopy with conventional antibodies and fluorescent proteins. Nat. Methods 13, 485–488 (2016)

    Article  Google Scholar 

  13. T. Ku et al., Multiplexed and scalable super-resolution imaging of three-dimensional protein localization in size-adjustable tissues. Nat. Biotechnol. 34, 973 (2016)

    Article  Google Scholar 

  14. Y. Zhao et al., Nanoscale imaging of clinical specimens using pathology-optimized expansion microscopy. Nat. Biotechnol. 35, 757 (2017)

    Article  Google Scholar 

  15. I.E. Wang, S.W. Lapan, M.L. Scimone, T.R. Clandinin, P.W. Reddien, Hedgehog signaling regulates gene expression in planarian glia. Elife 5, e16996 (2016)

    Google Scholar 

  16. T.J. Mosca, D.J. Luginbuhl, I.E. Wang, L. Luo, Presynaptic LRP4 promotes synapse number and function of excitatory CNS neurons. Elife 6, e27347 (2017)

    Google Scholar 

  17. L. Freifeld et al., Expansion microscopy of zebrafish for neuroscience and developmental biology studies. Proc. Natl. Acad. Sci. (2017). https://doi.org/10.1073/pnas.1706281114

    Article  Google Scholar 

  18. J.R. Crittenden et al., Striosome–dendron bouquets highlight a unique striatonigral circuit targeting dopamine-containing neurons. Proc. Natl. Acad. Sci. 113, 11318–11323 (2016)

    Article  Google Scholar 

  19. Y. Suofu et al., Dual role of mitochondria in producing melatonin and driving GPCR signaling to block cytochrome c release. Proc. Natl. Acad. Sci. 114, E7997–E8006 (2017)

    Article  Google Scholar 

  20. C.K. Cahoon et al., Superresolution expansion microscopy reveals the three-dimensional organization of the Drosophila synaptonemal complex. Proc. Natl. Acad. Sci. 114, E6857–E6866 (2017)

    Article  Google Scholar 

  21. T. Deshpande et al., Subcellular reorganization and altered phosphorylation of the astrocytic gap junction protein connexin43 in human and experimental temporal lobe epilepsy. Glia 65, 1809–1820 (2017)

    Article  Google Scholar 

  22. H.M.T. Choi, V.A. Beck, N.A. Pierce, Next-generation in situ hybridization chain reaction: higher gain, lower cost, greater durability. ACS Nano 8, 4284–4294 (2014)

    Article  Google Scholar 

  23. D. Cai, K.B. Cohen, T. Luo, J.W. Lichtman, J.R. Sanes, Improved tools for the Brainbow toolbox. Nat. Methods 10, 540–547 (2013)

    Article  Google Scholar 

Download references

Acknowledgements

This work was supported by Samsung Research Funding & Incubation Center for Future Technology (SRFC-IT1702-09). In addition, this work was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF-2017R1D1A1B03035340, NRF-2017R1A6A1A03015642) and the Ministry of Science, ICT & Future Planning (NRF-2017M3C7A1043841).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Jae-Byum Chang .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Nature Singapore Pte Ltd.

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Chang, JB. (2019). Expansion Microscopy for Brain Imaging. In: Kao, FJ., Keiser, G., Gogoi, A. (eds) Advanced Optical Methods for Brain Imaging. Progress in Optical Science and Photonics, vol 5. Springer, Singapore. https://doi.org/10.1007/978-981-10-9020-2_13

Download citation

  • DOI: https://doi.org/10.1007/978-981-10-9020-2_13

  • Published:

  • Publisher Name: Springer, Singapore

  • Print ISBN: 978-981-10-9019-6

  • Online ISBN: 978-981-10-9020-2

  • eBook Packages: EngineeringEngineering (R0)

Publish with us

Policies and ethics