# Engineered Reactive Interfaces Enable Mass Spectrometry Imaging of Multiple Thiols for Decoding PFOS-Induced Redox Dysregulation

## TL;DR

A new method improves the imaging of thiols in tissues, helping to understand how PFOS exposure affects redox balance and causes kidney damage.

## Contribution

A reactive interface-assisted derivatization platform enhances thiol detection sensitivity and spatial mapping fidelity in mass spectrometry imaging.

## Key findings

- The method enables sensitive profiling of multiple thiols like cysteine and glutathione in various tissues.
- PFOS exposure was shown to cause redox dysregulation and distinct thiol distribution patterns in the kidney.
- The sandwich structure reduces ion suppression and improves reaction efficiency for better imaging.

## Abstract

Spatial profiling of multiple thiols shows great significance
in
elucidating the redox status across tissue microregions and understanding
the molecular mechanisms of oxidative stress injury. Traditional matrix-assisted
laser desorption/ ionization mass spectrometry imaging (MALDI MSI)
relies on chemical derivatization for thiol visualization, but multistep
derivatization protocols and nonspecific matrix-adduct formation compromise
both detection sensitivity and spatial mapping fidelity. Herein, we
engineer a reactive interface-assisted chemical derivatization platform
for sensitive assessment of multiple thiols in various tissues via
forming the “matrix-tissue-interface” sandwich structure.
Reactive interface that predeposited with N-(9-Acridinyl)
maleimide (NAM) probes enables profile multiple thiols including cysteamine
(MEA), cysteine (Cys), cysteinyl-glycine (Cys–Gly), glutathione
(GSH), and ergothioneine (ET) across various tissues. The increased
sensitivity is likely due to the accelerated reaction efficiency that
arises from the locally high NAM concentrations in the tissue–NAM
interface, coupled with the sandwich architecture that mitigates ion
suppression of NAM probes and prevents matrix–NAM interaction.
The results demonstrated distinct tissue-specific distribution patterns
of various thiols as well as redox dysregulation of kidney induced
by PFOS exposure. This innovative MSI methodology offers a robust
route to enhance the derivatization performance for low-abundance
molecule imaging, facilitating the investigation of oxidative stress-related
disease mechanisms and the toxicological effects of pollutant.