Mechanical Characterization of Amyloid Fibrils Using Coarse‐Grained Normal Mode Analysis

Abstract

Recent experimental studies have shown that amyloid fi bril formed by aggregation of β peptide exhibits excellent mechanical properties comparable to other protein materials such as actin fi laments and microtubules. These excellent mechanical properties of amyloid fi brils are related to their functional role in disease expression. This indicates the necessity of understanding how an amyloid fi bril achieves the remarkable mechanical properties through self-aggregation with structural hierarchy. However, the structure-property-function relationship still remains elusive. In this work, the mechanical properties of human islet amyloid polypeptide (hIAPP) are studied with respect to its structural hierarchies and structural shapes by coarse-grained normal mode analysis. The simulation shows that hIAPP fi bril can achieve the excellent bending rigidity via specifi c aggregation patterns such as antiparallel stacking of β peptides. Moreover, the length-dependent mechanical properties of amyloids are found. This length-dependent property has been elucidated from a Timoshenko beam model that takes into account the shear effect on the bending of amyloids. In summary, the study sheds light on the importance of not only the molecular architecture, which encodes the mechanical properties of the fi bril, but also the shear effect on the mechanical (bending) behavior of the fi bril.

Influence of Aromatic Residues on the Material Characteristics of Aβ Amyloid Protofibrils at the Atomic Scale

“…[29] From their studies, the lowest frequency bending mode behavior was found to be similart ot he bending mode behavior of our model. In addition, the general trend of our resultsi sc onsistent with otherh IAPP results obtained by using the ENM methodb yY oon et al [70] Based on the vibrational analysis on ENM-converted hIAPP fibrils, the lowest bending modes were observed. The elastic modulusw as then obtained by relating the continuum mechanics with the correspondingd eformation-mode eigenvalues.…”

“…Previously,Y oon et al revealed the bending modes of hIAPP amyloid fibrils at the lowest frequencies. [54,70] To rsion and axial modes of hIAPP amyloid fibrils were also observed at higher frequencies.O ur resultss how similart endencies for bending and axial modes. In these modes, naturalf requencies reachedv alues in the ranges of 0.04-0.2 THz and 0.25-0.5 THz, respectively.H owever,a nalysiso ft he torsional mode gave different results to those obtained by Yoon et al;i nt his case, the torsional frequencies show lower values than those of the hIAPP amyloid fibrils.…”

Relationship between structural composition and material properties of polymorphic hIAPP fibrils

“…Furthermore, the role of hydrophobic amino acids could be presented through the differences between the homo and hetero models, including parallel and antiparallel models. In contrast to time-force curves, material responses would be different and reflected the previous study, which revealed the polymorphic characteristics of hIAPP fibrils by solving eigenvalue problems [29].…”

“…In our previous studies, we showed the material properties and characteristics of polymorphic hIAPP fibrils, which were evaluated via different types of deformation modes such as soft bending, stiff bending, torsion, and axial, using eigenvalue problems with ENM (elastic network model) and MD simulations [28,29]. Moreover, recently we studied the different material behaviors of hIAPP fibrils using constant bending simulations [30,31].…”

Structure-Property Relationship of Amyloidogenic Prion Nanofibrils

“…They also applied ENM to calculate the mechanical properties of hIAPP amyloid fibrils. Despite this detailed chemical interaction information, each structure exhibited different mechanical properties related to differences in H-bond interactions [61]. Additionally, the effects of mutations on the mechanical properties of amyloid fibrils [62] or multi-strand effects can be calculated [63].…”