Oligomeric and fibrillar amyloids, which cause neurodegenerative diseases, are typically formed through repetitive fracture and elongation processes involving single homogeneous amyloid monomers.

For several decades, various nanomaterials have been used in a wide range of industrial fields, research areas, and commercial products. Among many nanomaterials, nano-sized mercury materials are one of the most widely used nanomaterials in real life. However, due to the high toxicity of Hg(2+), it is imperative to develop an effective and practical detection method for Hg(2+) to protect human health and environment. In this study, a highly sensitive, label-free method of detecting Hg(2+) that requires only a single drop of solution was developed. The detection mechanism is based on the different surface potential arising from Hg(2+) binding to mismatched thymine-thymine sequences, creating a very stable base pair. The surface potential is measured with Kelvin probe force microscopy (KPFM) to a molecular resolution. The developed method is capable of detecting 2 fmol of Hg(2+), which is 500 times more sensitive than previously reported techniques. Moreover, our method can selectively detect Hg(2+) and can also be applied to tap water and river water. This KPFM-based Hg(2+) detection method can be used as an early detection technique for practical applications.

An actin filament is an essential cytoskeleton protein in a cell. Various proteins bind to actin for cell functions such as migration, division, and shape control. ADF/cofilin is a protein that severs actin filaments and is related to their dynamics. Actin is known to have excellent mechanical properties. Binding cofilin reduces its mechanical properties, and is related to the severing process. In this research, we applied a coarse-grained molecular dynamics simulation (CGMD) method to obtain actin filaments and cofilin-bound actin (cofilactin) filaments. Using these two obtained models, we constructed an elastic network model-based structure and conducted a normal mode analysis. Based on the low-frequency normal modes of the filament structure, we applied the continuum beam theory to calculate the mechanical properties of the actin and cofilactin filaments. The CGMD method provided structurally accurate actin and cofilactin filaments in relation to the mechanical properties, which showed good agreement with the established experimental results.

Various cytotoxic mechanisms for neurodegenerative disease are induced by specific conformations of Aβ intermediates. The efforts to understand the diverse intermediate forms of amyloid oligomers have been focused on understanding the aggregation mechanism of specific morphologies for Aβ intermediates. However, these are still not easy tasks to be accomplished because the diverse conformations of Aβ intermediates can be altered during the aggregation process, even though the same Aβ monomers are present. Thus, efforts to reveal the conformational change mechanism could be a fundamental process to understand the formation of diverse Aβ intermediate conformations. Here, we evaluate the conformational characteristics of Aβ fibrillar oligomers in different environments according to the length. We observed that Aβ fibrillar oligomers optimize their inherent hydrogen bonds and configurational entropy to stabilize their structure according to the simulation time and their length increase. In addition, we revealed the role of the expressed vibration mode shape in the fibrillar oligomers' elongation and deformation processes. Our results suggest that limitations in amyloid oligomer growth and transformations of their morphologies can be regulated and controlled by modifying the vibration features.

Amyloid fibrils are responsible for pathogenesis of various diseases and exhibit the structural feature of an ordered, hierarchical structure such as multi-stranded helical structure. As the multi-strandedness of amyloid fibrils has recently been found to be highly correlated with their toxicity and infectivity, it is necessary to study how the hierarchical (i.e. multi-stranded) structure of amyloid fibril is formed. Moreover, although it has recently been reported that the nanomechanics of amyloid proteins plays a key role on the amyloid-induced pathogenesis, a critical role that the multi-stranded helical structure of the fibrils plays in their nanomechanical properties has not fully characterized. In this work, we characterize the morphology and mechanical properties of multi-stranded amyloid fibrils by using equilibrium molecular dynamics simulation and elastic network model. It is shown that the helical pitch of multi-stranded amyloid fibril is linearly proportional to the number of filaments comprising the amyloid fibril, and that multi-strandedness gives rise to improving the bending rigidity of the fibril. Moreover, we have also studied the morphology and mechanical properties of a single protofilament (filament) in order to understand the effect of cross-β structure and mutation on the structures and mechanical properties of amyloid fibrils. Our study sheds light on the underlying design principles showing how the multi-stranded amyloid fibril is formed and how the structure of amyloid fibrils governs their nanomechanical properties.