Correlative optical photothermal infrared and X-ray fluorescence for chemical imaging of trace elements and relevant molecular structures directly in neurons

Abstract

Alzheimer’s disease (AD) is the most common cause of dementia, costing about 1% of the global economy. Failures of clinical trials targeting amyloid-β protein (Aβ), a key trigger of AD, have been explained by drug inefficiency regardless of the mechanisms of amyloid neurotoxicity, which are very difficult to address by available technologies. Here, we combine two imaging modalities that stand at opposite ends of the electromagnetic spectrum, and therefore, can be used as complementary tools to assess structural and chemical information directly in a single neuron. Combining label-free super-resolution microspectroscopy for sub-cellular imaging based on novel optical photothermal infrared (O-PTIR) and synchrotron-based X-ray fluorescence (S-XRF) nano-imaging techniques, we capture elemental distribution and fibrillary forms of amyloid-β proteins in the same neurons at an unprecedented resolution. Our results reveal that in primary AD-like neurons, iron clusters co-localize with elevated amyloid β-sheet structures and oxidized lipids. Overall, our O-PTIR/S-XRF results motivate using high-resolution multimodal microspectroscopic approaches to understand the role of molecular structures and trace elements within a single neuronal cell.

Using mid infrared to perform investigations beyond the diffraction limits of microcristalline pathologies: advantages and limitation of Optical PhotoThermal IR spectroscopy

“…Thanks to the opportunity offered by a commercial experimental set up device, numerous kinds of samples have been already investigated through OPT-IR spectroscopy encompassing submicrometer atmospheric particles [76], polymers [77], fragments from a historical painting [78] or nanocomposites [79]. Several exciting research works have also been published on biological samples [80][81][82][83][84][85][86][87][88][89]. Among them we can quote the possibility to discriminate different types of lung cells on histopathology glass slides [80], to determine relevant molecular structures directly in neurons [81] as well as the orientation of collagen in tendon [82].…”

“…Several exciting research works have also been published on biological samples [80][81][82][83][84][85][86][87][88][89]. Among them we can quote the possibility to discriminate different types of lung cells on histopathology glass slides [80], to determine relevant molecular structures directly in neurons [81] as well as the orientation of collagen in tendon [82].…”

Design and performance of a dedicated coherent X-ray scanning diffraction instrument at beamline NanoMAX of MAX IV

“…The instrument provides enough space for hosting compact sample environments, which contributes to its versatility. This endstation has been in user operation since summer 2017 and has produced impactful results in different fields of physics Nukala et al, 2021;Neckel et al, 2022), material science (Bjo ¨rling et al, 2020a;Dzhigaev et al, 2020Dzhigaev et al, , 2021Hammarberg et al, 2020;Ji et al, 2020;Marc ¸al et al, 2020Marc ¸al et al, , 2021Reimers et al, 2022;Li et al, 2022b) and biology (Silva Barreto et al, 2020;Gustavsson et al, 2021), using scanning and local approaches while exploiting scattering, fluorescence and coherent X-ray methods. It has also received considerable interest from communities of soft-matter physics (Nissila ¨et al, 2021;Huss-Hansen et al, 2022) and geology (Warlo et al, 2022) and has recently produced the first results of 3D ptychography in Bragg, demonstrating the great opportunities provided to crystal microscopy by the high coherent flux of fourth-generation sources (Li et al, 2022a).…”

Spatial Distribution of Intracellular Ion Concentrations in Aggregate‐Forming HeLa Cells Analyzed by μ‐XRF Imaging

“…It was applied to study a multitude of biological systems, including the elemental distribution in plants, [13] melanosomes, [14] juvenile barnacles, [15] and damselfly wings [16] . In particular, the distribution of biologically relevant elements was investigated for different cells, for example human neutrophils, [17] mouse embryonic fibroblast cells, [18] PC12 cells, [19] human cancer cells after treatment with drugs, [20–22] and Alzheimer‐affected brain cells [8,23,24] . Despite these applications of XRF for the assessment of Aβ subcellular localization and its amyloid‐specific ion enrichment, the XRF technique was so far, to the best of our knowledge, not used to resolve elemental distributions in other amyloid‐associated pathologies.…”