## 3 Results and Discussion
### Binding Interactions of Fibrillar Tau with TauRP1-14 Peptide
#### 3.7.2 Circular Dichroism Studies  
To gain insight into the secondary structural changes that occur in fibrillar Tau upon binding to the TauRP (1-14) peptide at varying concentrations, we conducted Circular Dichroism (CD) spectroscopy. The results can be seen in Table 6. Neat Tau fibrils revealed the presence of 44.3% \(\beta\)-sheet formation (comprising of both parallel and antiparallel beta sheets), 24.7% turns and 7.90% disordered structures. These data agree with previous studies showing that \(\beta\)-sheet formation was predominant in fibrillar tau [111]. Upon binding to the highest concentration of TauRP (1-14) (40 \(\upmu\)M), it was revealed that the secondary structure of Tau protein was altered. There was a significant increase in the disordered structural component, concomitantly with a decrease in helical, antiparallel and parallel beta-sheet and turn components. Interestingly, however, at lower concentrations (10 \(\upmu\)M and 20 \(\upmu\)M of TauRP (1-14)), it was observed that while the parallel beta-sheet component disappeared, and an increase in disordered structural component was observed; there was also an increase in anti-parallel beta-sheets. These results imply that the higher concentration (40 \(\upmu\)M) is likely the optimal concentration for disruption of the beta-sheet structures.  
The corresponding CD spectra (Figure 9) corroborate these results, where the neat Tau fibrils show a strong positive peak at 199.7 nm and a broad negative peak between 201 nm and 230 nm, with a maximum around 211 nm, which aligns with previous work, for the formation of heparin-induced Tau fibrils [112]. Upon binding to TauRP1-14, a shift was observed. At the lowest concentration (10 \(\upmu\)M), the positive peak was shifted to  
\begin{table}
\begin{tabular}{c c c c c} \hline \hline  & **Tau Fibrils** & \begin{tabular}{c} **Tau Fibrils** \\ **pre-Associated** \\ **with 10 \(\upmu\)M** \\ **TauRP1-14** \\ \end{tabular} & \
\begin{tabular}{c} **Tau Fibrils** \\ **pre-Associated** \\ **with 20 \(\upmu\)M** \\ **TauRP1-14** \\ \end{tabular} &
\begin{tabular}{c} **Tau Fibrils** \\ **pre-Associated** \\ **with 40 \(\upmu\)M** \\ **TauRP1-14** \\ \end{tabular} \\ \hline Helix & 23.1\% & 1.50\% & 0.00\% & 17.8\% \\ Antiparallel \(\beta\)-sheet & 17.8\% & 31.5\% & 37.5\% & 14.6\% \\ Parallel \(\beta\)-sheet & 26.5\% & 0.00\% & 0.00\% & 0.00\% \\ Turn & 24.7\% & 13.9\% & 14.1\% & 12.0\% \\ Disordered & 7.9\% & 53.1\% & 48.3\% & 55.6\% \\ \hline \hline \end{tabular}
\end{table}
Table 6: Secondary elements detected in CD spectra upon interactions with TauRP (1–14) with fibrillar Tau.  
Figure 8: (**a**) Tau fibrils grown at 37 \({}^{\circ}\)C. Scale bar = 1 \(\upmu\)m (inset = 100 nm). (**b**) Tau fibrils after association with to TauRP1-14 for 24 h. Scale bar = 500 nm.  
197.6 nm, while the negative peak was seen at 202.1 nm. As the concentration of TauRP1-14 was increased, the intensity of the negative peak continued to increase. The positive peak disappeared at the highest concentration of TauRP1-14 (40 \(\upmu\)M), indicative of the formation of increasingly disordered structures [113; 114]. Overall, our results show that the TauRP1-14 peptide is able to alter the conformation of fibrillar tau, particularly at the higher concentration.