Programme

O.7 -- Oral, VCTP-46

Date: Monday, 4 October 2021

Time: 16:30 - 16:50

Nanomechanical Stability of Aβ Tetramers and Fibril-like Structures: Molecular Dynamics Simulations

Adolfo B. Poma a,*,†, Tran Thi Minh Thub,c,e,*, Lam Tang Minh Tric,e, Hoang Linh Nguyenb,d,e, and Mai Suan Lif,†

a. Institute of Fundamental Technological Research, Polish Academy of Sciences, Pawińskiego 5B, 02-106, Warsaw b. Institute for Computational Science and Technology, SBI Building, Quang Trung Software City, Tan Chanh Hiep Ward, District 12, Ho Chi Minh City, Viet Nam c. Faculty of Materials Science and Technology, Ho Chi Minh City University of Science - VNUHCM, 227 Nguyen Van Cu Street, District 5, Ho Chi Minh City, Viet Nam d. Ho Chi Minh City University of Technology (HCMUT), Ho Chi Minh City 700000, Vietnam e. Vietnam National University, Ho Chi Minh City 700000, Vietnam f. Institute of Physics, Polish Academy of Sciences, Al. Lotników 32/46, 02-668 Warsaw, Poland

Alzheimer’s disease (AD) is a neurodegenerative disorder and one of the main causes of dementia. The disease is associated with amyloid beta (Aβ) peptide aggregation forming initial clusters, then fibril structure and plaques. Other neurodegenerative diseases such as type 2 diabetes, amyotrophic lateral sclerosis, and Parkinson’s disease follow a similar mechanism. Therefore, inhibition of Aβ aggregation is considered an effective way to prevent AD. Recent experiments have provided evidence that oligomers are more toxic agents than mature fibrils, prompting researchers to investigate various factors that may influence their properties. One of these factors is nanomechanical stability, which plays an important role in the self-assembly of Aβ and possibly other proteins. This stability is also likely to be related to cell toxicity. In this work, we compare the mechanical stability of Aβ-tetramers and fibrillar structures using a structure-based coarse grained (CG) approach and all-atom molecular dynamic simulation. Our results support the evidence for an increase in mechanical stability during the Aβ fibrillization process, which is consistent with in vitro AFM characterization of Aβ42 oligomers. Namely, using a coarse-grained model, we showed that the Young modulus of tetramers is lower than that of fibrils, and, as follows from the experiment, is about 1 GPa. Hydrogen bonds are the dominant contribution to the detachment of one chain from the Aβ fibril fragment. They tend to be more organized along the pulling direction, whereas in the Aβ tetramers no preference is observed.

Presenter: Tran Thi Minh Thu