Structural and Mechanical Properties of Amyloid Beta Fibrils: A Combined Experimental and Theoretical Approach

Abstract

In this combined experimental (deep ultraviolet resonance Raman (DUVRR) spectroscopy and atomic force microscopy (AFM)) and theoretical (molecular dynamics (MD) simulations and stress–strain (SS)) study, the structural and mechanical properties of amyloid beta (Aβ40) fibrils have been investigated. The DUVRR spectroscopy and AFM experiments confirmed the formation of linear, unbranched and β-sheet rich fibrils. The fibrils (Aβ40)n, formed using n monomers, were equilibrated using all-atom MD simulations. The structural properties such as β-sheet character, twist, interstrand distance, and periodicity of these fibrils were found to be in agreement with experimental measurements. Furthermore, Young’s modulus (Y) = 4.2 GPa computed using SS calculations was supported by measured values of 1.79 ± 0.41 and 3.2 ± 0.8 GPa provided by two separate AFM experiments. These results revealed size dependence of structural and material properties of amyloid fibrils and show the utility of such combined experimental and theoretical studies in the design of precisely engineered biomaterials.

Mapping the Broad Structural and Mechanical Properties of Amyloid Fibrils

“…2 and 4). model of Ab results in an exponential decay of the calculated Young's modulus, with the converged value matching the experimental one quite closely (48).…”

Adhesive behavior and detachment mechanisms of bacterial amyloid nanofibers

“…For these lower bound values, the Young's modulus is 0.14 GPa, which is one order of magnitude less than the lower bound of values reported for amyloid nanofibers. 46 The overall parametric range is fairly broad and should cover a variety of scenarios attainable with biological and engineered amyloid nanofibers. For simplicity, we normalized the parameters by their maximal values in reporting the results; hence, values ranged from 0 to 1.…”

Measurement of amyloid formation by turbidity assay—seeing through the cloud

“…Two such positive manifestations of amyloid include (1) the discovery of its role in maintaining the normal biological state as 'functional amyloid' (Greenwald and Riek 2010) and (2) amyloid’s potential in biosynthetic applications (Mitraki 2010; Raynes and Gerrard 2013). In this latter role, amyloid’s nanometer-scale dimensions (Xu et al 2016), its inherent capacity for autonomous self-assembly (Lee et al 2015; Sasahara et al 2010) and the desirable material properties of the nanofiber product (Paul et al 2016) all highlight the potential usefulness of amyloid as a ‘building block’ in nanotechnology applications (Rodina 2012). Due to their simplicity, turbidity assays will continue to be the ‘go to’ technique for monitoring amyloid formation across these disparate research areas.…”