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Microfluidic Protein Imaging Platform: Study of Tau Protein Aggregation and Alzheimer's Drug Response.

ABSTRACT: Tau protein aggregation is identified as one of the key phenomena associated with the onset and progression of Alzheimer's disease. In the present study, we performed on-chip confocal imaging of tau protein aggregation and tau-drug interactions using a spiral-shaped passive micromixing platform. Numerical simulations and experiments were performed in order to validate the performance of the micromixer design. We performed molecular modeling of adenosine triphosphate (ATP)-induced tau aggregation in order to successfully validate the concept of helical tau filament formation. Tau aggregation and native tau restoration were realized using an immunofluorescence antibody assay. The dose-response behavior of an Alzheimer's drug, methylthioninium chloride (MTC), was monitored on-chip for defining the optimum concentration of the drug. The proposed device was tested for reliability and repeatability of on-chip tau imaging. The amount of the tau protein sample used in our experiments was significantly less than the usage for conventional techniques, and the whole protein-drug assay was realized in less than two hours. We identified that intensity-based tau imaging could be used to study Alzheimer's drug response. In addition, it was demonstrated that cell-free, microfluidic tau protein assays could be used as potential on-chip drug evaluation tools for Alzheimer's disease.

SUBMITTER: Jain S

PROVIDER: S-EPMC7763324 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Microfluidic Protein Imaging Platform: Study of Tau Protein Aggregation and Alzheimer's Drug Response.

Jain Shubha S Swain Sarpras S Das Lopamudra L Swain Sarita S Giri Lopamudra L Kondapi Anand Kumar AK Narayanan Unni Harikrishnan H

Bioengineering (Basel, Switzerland) 20201213 4

Tau protein aggregation is identified as one of the key phenomena associated with the onset and progression of Alzheimer's disease. In the present study, we performed on-chip confocal imaging of tau protein aggregation and tau-drug interactions using a spiral-shaped passive micromixing platform. Numerical simulations and experiments were performed in order to validate the performance of the micromixer design. We performed molecular modeling of adenosine triphosphate (ATP)-induced tau aggregation ...[more]

PMID: 33322166

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Project description:The aggregates of microtubule-associated protein Tau are considered as a major hallmark of Alzheimer's disease. Tau aggregates accumulate intracellularly leading to neuronal toxicity. Numerous approaches have been targeted against Tau protein aggregation, which include application of synthetic and natural compounds. Toluidine blue is a basic dye of phenothiazine family, which on irradiation with a 630 nm light gets converted into a photoexcited form, leading to generation of singlet oxygen species. Methylene blue is the parent compound of toluidine blue, which has been reported to be potent against tauopathy. In the present work, we studied the potency of toluidine blue and photoexcited toluidine blue against Tau aggregation. Biochemical and biophysical analyses using sodium dodecyl sulfate-polyacrylamide gel electrophoresis, ThS fluorescence, circular dichroism spectroscopy, and electron microscopy suggested that toluidine blue inhibited the aggregation of Tau in vitro. The photoexcited toluidine blue potentially dissolved the matured Tau fibrils, which indicated the disaggregation property of toluidine blue. The cell biology studies including the cytotoxicity assay and reactive oxygen species (ROS) production assay suggested toluidine blue to be a biocompatible dye as it reduced ROS levels and cell death. The photoexcited toluidine blue modulates the cytoskeleton network in cells, which was supported by immunofluorescence studies of neuronal cells. The studies in a UAS Tau E14 transgenic Drosophila model suggested that photoexcited toluidine blue was potent to restore the survival and memory deficits of Drosophila. The overall finding of our studies suggested toluidine blue to be a potent molecule in rescuing the Tau-mediated pathology by inhibiting its aggregation, reducing the cell death, and modulating the tubulin levels and behavioral characteristics of Drosophila. Thus, toluidine blue can be addressed as a potent molecule against Alzheimer's disease.

Dataset Information

Microfluidic Protein Imaging Platform: Study of Tau Protein Aggregation and Alzheimer's Drug Response.

Publications

Microfluidic Protein Imaging Platform: Study of Tau Protein Aggregation and Alzheimer's Drug Response.

Similar Datasets

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