**4. Conclusions**

In this paper, we investigated the effect of Aβ monomers on the mechanical properties of the POPC vesicle. Additionally, we have investigated the change in basic membrane parameters, such as membrane thickness and APL. We showed that membrane thickness increases and APL decreases after the incorporation of Aβ. We postulate that this results from the bilayer's mechanical remodeling after Aβ monomer incorporation reported previously in the literature. We observed a decrease in the bending rigidity coefficient after incorporating Aβ in both MD simulation and the flicker-noise experiment. Since it was reported in the literature that Aβ-induced membrane remodeling is more likely when bending rigidity is smaller, we believe that the progressing decrease of bending rigidity might be considered a driving factor of neurodegeneration progression. We managed to prove that incorporating Aβ peptides influences the mechanical properties of lipid membranes, suggesting that membrane's mechanical properties may play a more important role in neurodegenerative disorders. Finally, we have investigated the difference in wave propagation on membranes with and without incorporated Aβ peptides. We showed that the presence of the peptides did change the behavior of the system. This could lead to an impediment of nerve impulse propagation and/or shift in membrane resonance frequency and, as a result, disrupt gamma oscillations. In summary, this paper aims to draw attention to an important hypothesis that mechanically driven molecular phenomena that originate from the membrane could be a critical factor in the pathogenesis of AD. We believe that we presented satisfactory results to support this claim. We acknowledge that this study was limited to the effect on POPC lipid membrane only. Further studies should be focused on more biologically relevant membranes, specifically on the disruption of their ability to cluster dynamically. The effect of mechanical changes on lipid metabolism/signaling should also be addressed in future studies.

**Supplementary Materials:** Supplementary materials can be found at https://www.mdpi.com/14 22-0067/22/1/18/s1, Supporting Information: (1) Peptide incorporation into planar POPC bilayer, (2) System setup for POPC vesicles with incorporated peptides, (3) Verification of Aβ incorporation in GUVs, (4) Bending rigidity measurements using flicker-noise spectroscopy.

**Author Contributions:** Conceptualization, D.D. and S.K.; methodology, D.D. and G.C.; software, D.D.; validation, D.D.; formal analysis, D.D.; investigation, D.D.; resources, D.D.; data curation, D.D.; writing—original draft preparation, D.D.; writing—review and editing, G.C. and S.K.; visualization, D.D.; supervision, S.K.; project administration, D.D.; funding acquisition, D.D. All authors have read and agreed to the published version of the manuscript.

**Funding:** This work was possible thanks to the financial support from the National Science Centre (Poland) grants Nos. 2016/21/N/NZ1/02767 and 2018/30/E/NZ1/00099.

**Data Availability Statement:** Most of the data is available in the manuscript supplementary information. The simulation data presented in this study are available on request from the corresponding author. This data are not publicly available due to GBs files sizes.

**Acknowledgments:** Numerical resources for Molecular Dynamics simulations were granted by Wroclaw Centre of Networking and Supercomputing, gran<sup>t</sup> No. 274.

**Conflicts of Interest:** The authors declare no conflict of interest.
