Correlative High-Resolution Imaging of Iron Uptake in Lung Macrophages
Artikel i vetenskaplig tidskrift, 2022

Detection of iron at the subcellular level in order to gain insights into its transport, storage, and therapeutic prospects to prevent cytotoxic effects of excessive iron accumulation is still a challenge. Nanoscale magnetic sector secondary ion mass spectrometry (SIMS) is an excellent candidate for subcellular mapping of elements in cells since it provides high secondary ion collection efficiency and transmission, coupled with high-lateral-resolution capabilities enabled by nanoscale primary ion beams. In this study, we developed correlative methodologies that implement SIMS high-resolution imaging technologies to study accumulation and determine subcellular localization of iron in alveolar macrophages. We employed transmission electron microscopy (TEM) and backscattered electron (BSE) microscopy to obtain structural information and high-resolution analytical tools, NanoSIMS and helium ion microscopy-SIMS (HIM-SIMS) to trace the chemical signature of iron. Chemical information from NanoSIMS was correlated with TEM data, while high-spatial-resolution ion maps from HIM-SIMS analysis were correlated with BSE structural information of the cell. NanoSIMS revealed that iron is accumulating within mitochondria, and both NanoSIMS and HIM-SIMS showed accumulation of iron in electrolucent compartments such as vacuoles, lysosomes, and lipid droplets. This study provides insights into iron metabolism at the subcellular level and has future potential in finding therapeutics to reduce the cytotoxic effects of excessive iron loading.

Iron uptake

Secondary ion mass spectrometry

Cytotoxic effects

NanoSIMS

Lung macrophages

Iron metabolism

Författare

Jelena Lovric

Chalmers, Kemi och kemiteknik, Kemi och biokemi

AstraZeneca AB

Neda Najafinobar

AstraZeneca AB

Chalmers, Kemi och kemiteknik, Kemi och biokemi

Michael Kurczy

Chalmers, Kemi och kemiteknik, Kemi och biokemi

AstraZeneca AB

Olivier De Castro

Luxembourg Institute of Science and Technology

Antje Biesemeier

Luxembourg Institute of Science and Technology

Lena von Sydow

AstraZeneca AB

Magnus Klarqvist

AstraZeneca AB

T. Wirtz

Luxembourg Institute of Science and Technology

Per Malmberg

Chalmers, Kemi och kemiteknik, Kemi och biokemi

Analytical Chemistry

0003-2700 (ISSN) 1520-6882 (eISSN)

Vol. 94 37 12798-12806

Ämneskategorier

Acceleratorfysik och instrumentering

Annan medicinteknik

Atom- och molekylfysik och optik

Styrkeområden

Hälsa och teknik

Infrastruktur

Infrastruktur för kemisk avbildning

DOI

10.1021/acs.analchem.2c02675

PubMed

36070604

Mer information

Senast uppdaterat

2024-03-07