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

作　　者：Jian Zhao Lulu Jiang Alex Matlock Yihong Xu Jiabei Zhu Hongbo Zhu Lei Tian Benjamin Wolozin Ji-xin Cheng 

机构地区：[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

出　　处：《Light(Science & Applications)》2023年第7期1354-1369,共16页光（科学与应用)（英文版）

基　　金：supported by the National Institute of General Medical Sciences(R35GM136223);a grant from Daylight Solutions,and a grant(2023-321163);the Chan Zuckerberg Initiative Donor-Advised Fund at the Silicon Valley Community Foundation.

摘　　要：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 midinfrared 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 fbrils,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 theβ-sheet for tau fibril structure is achieved.

关 键 词：TAU AMYLOID chemical 

分 类 号：O4[理学—物理]