Micro Mechanical Properties of Model Alzheimer's Beta Amyloid Fibrils

Abstract

Protein nanofibrils are the ordered end product in the protein self-association process. Firstly recognized as linked to amyloid diseases, including Alzheimer's, they are currently identified as remarkably stable states accessible to almost any polypeptide chain. Interestingly enough, protein nanofibrils made of the same polypeptide building blocks adopt different ordered three dimensional structures. The purpose of this study is to investigate via all-atom molecular dynamics simulations the micromechanical properties of model Alzheimer's B(9-40)-amyloid fibrils that display different quaternary structure. These structures consisted of a three-fold symmetric model1 and a striated-ribbon pattern2. We found that the Young's modulus value of the model fibril structures both fall in the range of 108 Pa, consistent with values found in the literature, with the striated-ribbon structure being more flexible than the three-fold symmetric model. We propose possible relationships between the geometry of the fibril and the interactions that govern structure stability.Footnotes1 Paravastu AK, Leapman RD, Yau WM, Tycko R. Molecular structural basis for polymorphism in Alzheimer's beta-amyloid fibrils. Proc Natl Acad Sci U S A. 2008 Nov 25;105(47):18349-54.2 Petkova AT, Yau WM, Tycko R. Experimental constraints on quaternary structure in Alzheimer's beta-amyloid fibrils. Biochemistry. 2006 Jan 17;45(2):498-512.