Mid-infrared chemical imaging of intracellular tau fibrils using fluorescence-guided computational photothermal microscopy

Jian Zhao; Lulu Jiang; Alex Matlock; Yihong Xu; Jiabei Zhu; Hongbo Zhu; Lei Tian; Benjamin Wolozin; Ji-Xin Cheng

doi:10.1038/s41377-023-01191-6

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Mid-infrared chemical imaging of intracellular tau fibrils using fluorescence-guided computational photothermal microscopy

Original Articles

- Mid-infrared chemical imaging of intracellular tau fibrils using fluorescence-guided computational photothermal microscopy
- Light: Science & Applications Vol. 12, Issue 7, Pages: 1354-1369(2023)
- Affiliations：
  
  1.Department of Electrical and Computer Engineering, Boston University, Boston, MA 02215, USA
  2.The Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA 02142, USA
  3.Department of Pharmacology and Experimental Therapeutics, Boston University School of Medicine, Boston, MA 02118, USA
  4.Department of Physics, Boston University, Boston, MA 02215, USA
  5.State Key Laboratory of Luminescence and Applications, Changchun Institute of Optics, Fine Mechanics and Physics, Chinese Academy of Sciences, 130033 Changchun, China
  6.Department of Biomedical Engineering, Boston University, Boston, MA 02215, USA
  7.Photonics Center, Boston University, Boston, MA 02215, USA
  8.Present address: Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02142, USA
- Author bio：
  
  Jian Zhao (jianzhao@knights.ucf.edu)
  Ji-Xin Cheng (jxcheng@bu.edu)
- Funds：
- DOI：10.1038/s41377-023-01191-6
  CLC：
- Published：31 July 2023，
  
  Published Online：15 June 2023，
  
  Received：22 February 2023，
  
  Revised：18 May 2023，
  
  Accepted：21 May 2023
- Accepted：
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Zhao, J. et al. Mid-infrared chemical imaging of intracellular tau fibrils using fluorescence-guided computational photothermal microscopy. Light: Science & Applications, 12, 1354-1369 (2023).
DOI：

Zhao, J. et al. Mid-infrared chemical imaging of intracellular tau fibrils using fluorescence-guided computational photothermal microscopy. Light: Science & Applications, 12, 1354-1369 (2023). DOI： 10.1038/s41377-023-01191-6.

摘要

Abstract

Amyloid proteins are associated with a broad spectrum of neurodegenerative diseases. However

it remains a grand challenge to extract molecular structure information from intracellular amyloid proteins in their native cellular environment. To address this challenge

we developed a computational chemical microscope integrating 3D mid-infrared photothermal imaging with fluorescence imaging

termed Fluorescence-guided Bond-Selective Intensity Diffraction Tomography (FBS-IDT). Based on a low-cost and simple optical design

FBS-IDT enables chemical-specific volumetric imaging and 3D site-specific mid-IR fingerprint spectroscopic analysis of tau fibrils

an important type of amyloid protein aggregates

in their intracellular environment. Label-free volumetric chemical imaging of human cells with/without seeded tau fibrils is demonstrated to show the potential correlation between lipid accumulation and tau aggregate formation. Depth-resolved mid-infrared fingerprint spectroscopy is performed to reveal the protein secondary structure of the intracellular tau fibrils. 3D visualization of the β-sheet for tau fibril structure is achieved.

关键词

Keywords

references

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