# Mid-infrared Chemical Imaging of Intracellular Tau Fibrils using Fluorescence-guided Computational Photothermal Microscopy

## TL;DR

This paper introduces a novel fluorescence-guided computational microscopy technique that enables 3D chemical imaging and spectroscopic analysis of intracellular tau fibrils, revealing their structure and relation to lipids in native cells.

## Contribution

The development of FBS-IDT, a low-cost, label-free 3D imaging method combining mid-IR photothermal and fluorescence imaging for intracellular amyloid analysis.

## Key findings

- Successful 3D visualization of tau fibril structures.
- Correlation between lipid accumulation and tau aggregation.
- Revealed protein secondary structure of tau fibrils.

## 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 \b{eta}-sheet for tau fibril structure is achieved.

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Source: https://tomesphere.com/paper/2302.11769