Neuronal Tau Protein Film Stability on Gold Surface: Electrochemical Impedance Spectroscopy of Partial and Complete Surfaces
Bibliographic record
Abstract
Tau is a neuronal protein responsible for microtubule formation [1]. It is also the pathological protein active in the Alzheimer’s Disease (AD) pathway. When Tau begins to aggregate as a result of misfolding, the neuronal cells die due to the lack of microtubule formation and can take on prion-like properties [2]. Therefore, detection of aggregated Tau can serve as a powerful tool in the early diagnosis of AD and dementia related diseases. As has been previously demonstrated, Tau 441 can be detected with an electrochemical immunoassay based on the electrochemical impedance spectroscopy (EIS) by using gold electrode [3]. The EIS was also used to monitor interactions between Tau protein and Heparin [4]. Due to the sensitive nature of protein molecules, buffers of physiological pH need to be employed to maintain native protein structure. However, not all buffer solutions are appropriately suited for surface studies. Herein, we describe use of EIS to monitor and detect surface stability of Tau protein films on gold electrode in two common buffers: MES buffer and Phosphate Buffer (PB). Additionally, the stability of partial and complete surfaces was also monitored. The partial surface was completed by backfilling with a solution of bovine serum albumin (BSA) and the complete surface was backfilled using 1-butylamine and hexanethiol. After modifying the surface of the electrode with activated lipoic acid and Tau, a series of further incubation steps were performed to test surface stability under various conditions. The EIS was measured as a function of Tau or Heparin concentrations, and incubation time and temperature. The control experiments included, Tau-free surface, Heparin-free solution, and buffer solutions in order to minimize non-specific interactions. The stability of the surfaces was measured as a signal change in EIS after incubations and it was discovered that certain buffered solutions and partial surfaces induced large changes in tau protein films on surfaces. References [1] M.D. Weingarten, A.H. Lockwood, S. Hwo, M.W. Kirschner, A Protein Factor Essential for Microtubule Assembly, Natl. Acad Sci. 72 (1975) 1858–1862. [2] F. Clavaguera, J. Hench, M. Goedert, M. Tolnay, Prion-like transmission and spreading of tau pathology, Neuropathol. Appl. Neurobiol. 41 (2015) 47–58. [3] N. Carlin, S. Martic-Milne, Anti-tau antibodies based electrochemical sensor for detection of tau protein biomarkers, J. Electrochem. Soc. 165 (2018) G3018–G3025. [4] H. Trzeciakiewicz, J. Esteves-Villanueva, R. Soudy, K. Kaur, S. Martic-Milne, Electrochemical characterization of protein adsorption onto YNGRT-Au and VLGXE-Au surfaces, Sensors (Switzerland). 15 (2015) 19429–19442.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".