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Diamond Quantum Sensing Revealing the Relation between Free Radicals and Huntington's Disease.

ABSTRACT: Huntington's disease (HD) is a well-studied yet rare disease caused by a specific mutation that results in the expression of polyglutamine (PolyQ). The formation of aggregates of PolyQ leads to disease and increases the level of free radicals. However, it is unclear where free radicals are generated and how they impact cells. To address this, a new method called relaxometry was used to perform nanoscale MRI measurements with a subcellular resolution. The method uses a defect in fluorescent nanodiamond (FND) that changes its optical properties based on its magnetic surroundings, allowing for sensitive detection of free radicals. To investigate if radical generation occurs near PolyQ aggregates, stable tetracycline (tet)-inducible HDQ119-EGFP-expressing human embryonic kidney cells (HEK PQ) were used to induce the PolyQ formation and Huntington aggregation. The study found that NDs are highly colocalized with PolyQ aggregates at autolysosomes, and as the amount of PolyQ aggregation increased, so did the production of free radicals, indicating a relationship between PolyQ aggregation and autolysosome dysfunction.

SUBMITTER: Fan S

PROVIDER: S-EPMC10375573 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature

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Diamond Quantum Sensing Revealing the Relation between Free Radicals and Huntington's Disease.

Fan S S Nie L L Zhang Y Y Ustyantseva E E Woudstra W W Kampinga H H HH Schirhagl R R

ACS central science 20230621 7

Huntington's disease (HD) is a well-studied yet rare disease caused by a specific mutation that results in the expression of polyglutamine (PolyQ). The formation of aggregates of PolyQ leads to disease and increases the level of free radicals. However, it is unclear where free radicals are generated and how they impact cells. To address this, a new method called relaxometry was used to perform nanoscale MRI measurements with a subcellular resolution. The method uses a defect in fluorescent nanod ...[more]

PMID: 37521781

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Project description:Naturally occurring paramagnetic species (PS), such as free radicals and paramagnetic metalloproteins, play an essential role in a multitude of critical physiological processes including metabolism, cell signaling, and immune response. These highly dynamic species can also act as intrinsic biomarkers for a variety of disease states, while synthetic paramagnetic probes targeted to specific sites on biomolecules enable the study of functional information such as tissue oxygenation and redox status in living systems. The work presented herein describes a new sensing method that exploits the spin-dependent emission of photoluminescence (PL) from an ensemble of nitrogen-vacancy centers in diamond for rapid, nondestructive detection of PS in living systems. Uniquely this approach involves simple measurement protocols that assess PL contrast with and without the application of microwaves. The method is demonstrated to detect concentrations of paramagnetic salts in solution and the widely used magnetic resonance imaging contrast agent gadobutrol with a limit of detection of less than 10 attomol over a 100 μm × 100 μm field of view. Real-time monitoring of changes in the concentration of paramagnetic salts is demonstrated with image exposure times of 20 ms. Further, dynamic tracking of chemical reactions is demonstrated via the conversion of low-spin cyanide-coordinated Fe3+ to hexaaqua Fe3+ under acidic conditions. Finally, the capability to map paramagnetic species in model cells with subcellular resolution is demonstrated using lipid membranes containing gadolinium-labeled phospholipids under ambient conditions in the order of minutes. Overall, this work introduces a new sensing approach for the realization of fast, sensitive imaging of PS in a widefield format that is readily deployable in biomedical settings. Ultimately, this new approach to nitrogen vacancy-based quantum sensing paves the way toward minimally invasive real-time mapping and observation of free radicals in in vitro cellular environments.

Dataset Information

Diamond Quantum Sensing Revealing the Relation between Free Radicals and Huntington's Disease.

Publications

Diamond Quantum Sensing Revealing the Relation between Free Radicals and Huntington's Disease.

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