Nanomechanical properties of single amyloid fibrils

Abstract

Amyloid fibrils are traditionally associated with neurodegenerative diseases like Alzheimer's disease, Parkinson's disease or Creutzfeldt-Jakob disease. However, the ability to form amyloid fibrils appears to be a more generic property of proteins. While disease-related, or pathological, amyloid fibrils are relevant for understanding the pathology and course of the disease, functional amyloids are involved, for example, in the exceptionally strong adhesive properties of natural adhesives. Amyloid fibrils are thus becoming increasingly interesting as versatile nanobiomaterials for applications in biotechnology. In the last decade a number of studies have reported on the intriguing mechanical characteristics of amyloid fibrils. In most of these studies atomic force microscopy (AFM) and atomic force spectroscopy play a central role. AFM techniques make it possible to probe, at nanometer length scales, and with exquisite control over the applied forces, biological samples in different environmental conditions. In this review we describe the different AFM techniques used for probing mechanical properties of single amyloid fibrils on the nanoscale. An overview is given of the existing mechanical studies on amyloid. We discuss the difficulties encountered with respect to the small fibril sizes and polymorphic behavior of amyloid fibrils. In particular, the different conformational packing of monomers within the fibrils leads to a heterogeneity in mechanical properties. We conclude with a brief outlook on how our knowledge of these mechanical properties of the amyloid fibrils can be exploited in the construction of nanomaterials from amyloid fibrils.

Molecular, Local, and Network-Level Basis for the Enhanced Stiffness of Hydrogel Networks Formed from Coassembled Racemic Peptides: Predictions from Pauling and Corey

“…However, the small widths (∼3 nm) of the racemic fibrils make it incredibly difficult to measure their stiffness by established methods such as atomic force microscopy (AFM). 59,60 Thus, we turned our attention to diffusing wave spectroscopy (DWS). 61−63 DWS offers a noninvasive method to access the high frequency linear rheology of biomaterials, beyond the capabilities of conventional mechanical rheometers and particle tracking microrheology methods, enabling precise characterization of their mechanical properties.…”

Computational integration of nanoscale physical biomarkers and cognitive assessments for Alzheimer’s disease diagnosis and prognosis

“…To date, few studies have been performed for investigating the nanomechanical properties of proteins implicated in AD ( 27 , 36 , 37 ). This is most likely due to challenges associated with quantitatively characterizing 1000 + CSF proteins ( 38 ) and then subsequently associating their physical characteristics with AD pathogenesis.…”

Implications of peptide assemblies in amyloid diseases

“…241 The cross-section of individual αS monomers in the fold was trapezoid instead of circular, resulting in a two-fold increase in moment of inertia (Sweers 2012). 263 Though not substantiated, such non-circular packing of monomers could also hold true for other β-sheet folded proteins. 261, 263 In addition, curly αS fibrils prepared by filtration-like steps during aggregation possessed a persistence length of 170 nm, while straight αS fibrils from unperturbed aggregation displayed persistence lengths of up to 140 μm.…”