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

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

Gwonchan Yoon, Jinhak Kwak, Jae In Kim, Sungsoo Na, and Kilho Eom

Abstract

Recentexperimental studies have shown that amyloid fibril formed by aggregation of βpeptide exhibits excellent mechanical properties comparable to other proteinmaterials such as actin filaments and microtubules. These excellent mechanicalproperties of amyloid fibrils are related to their functional role in diseaseexpression. This indicates the necessity to understand how an amyloid fibrilachieves the remarkable mechanical properties through self-aggregation withstructural hierarchy, highlighting the structure-property-function relationshipfor amyloids, whereas such relationship still remains elusive. In this work, wehave studied the mechanical properties of human islet amyloid polypeptide(hIAPP) with respect to its structural hierarchies and structural shapes bycoarse-grained normal mode analysis. Our simulation shows that hIAPP fibril canachieve the excellent bending rigidity via specific aggregation pattern such asantiparallel stacking of β peptides. Moreover, we have found thelength-dependent mechanical properties of amyloids. This length-dependentproperty has been elucidated from Timoshenko beam model that takes into accountthe shear effect on the bending of amyloids. In summary, our study sheds lighton the importance of not only the molecular architecture, which encodes themechanical properties of the fibril, but also the shear effect on themechanical (bending) behavior of the fibril.

This manuscript will appear at Advanced Functional Materials.