Nanomechanical Properties of Polymorphic Human Islet Amyloid Polypeptide Protofibrils in the Multiple Physiological and Mechanical Conditions

Abstract

Fibrillar and oligomeric amyloids are the origin of neuro-degenerative and degenerative diseases as type II diabetes, Alzheimer's diseases, and so forth. The common properties of amyloids are located near functional cells, not easily degraded, and disrupt their own functions. These amyloids had polymorphic characteristics under physiological conditions such as thermal effect, pH, ionic strength, metal ions and internal fluctuations. Developed from denatured and misfolded amyloid monomers, polymorphic amyloids are mainly existed as parallel or antiparallel composition along to fibril axis and lateral thickness composition by adding unit amyloid protofilament through the experimental techniques. Despite experimental effort of polymorphic structures of amyloid proteins, there are some lacks of knowledge that relationship between structural composition of polymorphic amyloids and their stabilities in detail. The mechanical characterization as bending, stretching can give insight for understanding the structure-property relationship of amyloid protofilaments. Considering that amyloids are developed through the repetitive fragmentation and elongation mechanisms, it is crucial to understand the structural stabilities of polymorphic amyloid protofibrils. Here, we reported the polymorphic characteristics of hIAPP amyloid protofibrils in mechanical insight via equilibrium and steered molecular dynamics (MD and SMD). Through the principal component analysis of polymorphic hIAPP protofibrils after equilibrium MD simulations, we found the different deformation mode (i.e. bending, stretching and torsion) of polymorphic hIAPP protofibrils. Using eigenvalue analysis, antiparallel models had considerable structural stability than parallel models due to the asymmetric hydrogen bond network composition. Furthermore, by applying the constant force bending and constant velocity tensile SMD simulations, we found the dominant material characteristics that homo composition had ductile feature, while hetero composition had brittle characteristics. We provide the relationship between structural composition and their properties, which are related to growth mechanism of amyloids. Our study also provides the possibilities for the basic template for functional biomaterials in the future.