Abstract
Examining chemical and structural characteristics of micro-features in complex tissue matrices is essential for understanding biological systems. Advances in multimodal chemical and structural imaging using synchrotron radiation have overcome many issues in correlative imaging, enabling the characterization of distinct microfeatures at nanoscale resolution in ex vivo tissues. We present a nanoscale imaging method that pairs X-ray ptychography and X-ray fluorescence microscopy (XFM) to simultaneously examine structural features and quantify elemental content of microfeatures in complex ex vivo tissues. We examined the neuropathological microfeatures Lewy bodies, aggregations of superoxide dismutase 1 (SOD1) and neuromelanin in human post-mortem Parkinson's disease tissue. Although biometals play essential roles in normal neuronal biochemistry, their dyshomeostasis is implicated in Parkinson's disease aetiology. Here we show that Lewy bodies and SOD1 aggregates have distinct elemental fingerprints yet are similar in structure, whilst neuromelanin exhibits different elemental composition and a distinct, disordered structure. The unique approach we describe is applicable to the structural and chemical characterization of a wide range of complex biological tissues at previously unprecedented levels of detail.
Highlights
Multimodal imaging methods can provide information about the structural and chemical composition of biological specimens
We focused on three insoluble microfeatures involved in oxidative stress cascades of molecular neurodegeneration in Parkinson's disease (PD); Lewy bodies (LB), superoxide dismutase 1 (SOD1) protein deposits and neuromelanin (NM).[3]
We examined a separate population of proteinaceous aggregates we recently described in the degenerating substantia nigra (SN) of the PD brain which contain misfolded SOD1 protein.[8]
Summary
Multimodal imaging methods can provide information about the structural and chemical composition of biological specimens. Current methods require quanti ed regions of interest to be identi ed separately for each modality, and necessitate varying sample preparation methods, both of which may compromise data quality These limitations lower the speci city and sensitivity of these approaches, for nanoscale imaging of complex ex vivo tissue samples. We present a method involving advances in synchrotron imaging technology and increasingly brilliant light sources, enabling multimodal nanoscale structural and chemical characterization of a wide range of complex biological tissues at previously unprecedented levels of detail in their native state. We apply this method to interrogate disease-associated microfeatures in fresh frozen human brain tissues. Subcellular imaging of human post-mortem tissues provides insights into the biochemical mechanisms that underlie the formation of these pathological features in disease processes[2] and is more widely applicable to other disease states and tissues
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