Advances in AFM Imaging Applications for Characterizing the Biophysical Properties of Amyloid Fibrils

Abstract

Although the formation mechanism of amyloid fibrils in bodies is still debated, it has recently been reported how amyloid fibrils can be formed in vitro. Accordingly, we have gained a better understanding of the self-assembly mechanism and intrinsic properties of amyloid fibrils. Because the structure of amyloid fibrils consists of nanoscaled insoluble strands (a few nanometers in diameter and micrometers long), a special tool is needed to study amyloid fibrils at length. Atomic force microscopy (AFM) is supposed to be a versatile toolkit to probe such a tiny biomolecule. The physical/chemical properties of amyloid fibrils have been explored by AFM. In particular, AFM enables the visualization of amyloid fibrillation with different incubation times as well as the concentrations of the formed amyloid fibrils as affected by fibril diameters and lengths. Very recently, the minute structural changes and/or electrical properties of amyloid fibrils have been made by using advanced AFM techniques including dynamic liquid AFM, PeakForce QNM (quantitative nanomechanical mapping), and Kelvin probe force microscopy (KPFM). Herein, we summarize the biophysical properties of amyloid fibrils that are newly discovered with the help of those advanced AFM techniques and suggest our perspectives and future directions for the study of amyloid fibrils.

Hierarchical approach for the rational construction of helix-containing nanofibrils using α,β-peptides

“…The observed fluctuation in the height of fibrils can be a sign of different stages of peptide aggregation, as mentioned above. 61 TEM analysis confirmed the pattern of nanostructure formation in water, starting from globular aggregates to fibrils, after a short period of time (Fig. 8).…”

Microwave-induced formation of oligomeric amyloid aggregates

“…For several decades, many synthetic approaches have been developed to understand the mechanism of amyloid aggregate formation in the brains of patients diagnosed with neurodegenerative diseases such as Alzheimer's and Parkinson's diseases [1][2][3][4]. As a conventional heating method, irradiation of the amyloid solution with thermal energy at various temperatures ranging from 37 °C-120 °C has been attempted depending on the features of specific amyloid proteins [5][6][7]. For example, amyloid-β and α-synuclein have generally been reacted at around 37 °C [8][9][10][11].…”

Nanomechanics of Pectin-Linked β-Lactoglobulin Nanofibril Bundles

“…Atomic force microscopy (AFM) is a unique class of techniques in which samples are probed with a fine tip that is held, pushed into, or moved over the sample surface. − It can produce three-dimensional images but can also probe mechanical properties by pressing the AFM tip into structures with sufficient force to deform them (nanoindentation) or allowing polymers to adhere to the tip and then withdrawing it until they are pulled apart (force spectroscopy). These and other approaches are illustrated in Volpatti and Knowles …”