Granular Assembly of α-Synuclein Leading to the Accelerated Amyloid Fibril Formation with Shear Stress

α-Synuclein participates in the Lewy body formation of Parkinson's disease. Elucidation of the underlying molecular mechanism of the amyloid fibril formation is crucial not only to develop a controlling strategy toward the disease, but also to apply the protein fibrils for future biotechnology. Discernable homogeneous granules of α-synuclein composed of approximately 11 monomers in average were isolated in the middle of a lag phase during the in vitro fibrillation process. They were demonstrated to experience almost instantaneous fibrillation during a single 12-min centrifugal membrane-filtration at 14,000×g. The granular assembly leading to the drastically accelerated fibril formation was demonstrated to be a result of the physical influence of shear force imposed on the preformed granular structures by either centrifugal filtration or rheometer. Structural rearrangement of the preformed oligomomeric structures is attributable for the suprastructure formation in which the granules act as a growing unit for the fibril formation. To parallel the prevailing notion of nucleation-dependent amyloidosis, we propose a double-concerted fibrillation model as one of the mechanisms to explain the in vitro fibrillation of α-synuclein, in which two consecutive concerted associations of monomers and subsequent oligomeric granular species are responsible for the eventual amyloid fibril formation

Gift politics: Exposure and surveillance in the anthropocene

This article discusses the role of gift relations in the Anthropocene. We reinterpret Mauss’s original concept of the gift to understand its application and transformation in a social context that increasingly sees human behavior as a resource for the realization of governmental and corporate objectives. Contemporary gift rela- tions focus on reciprocity through personal data instead of physical artifacts, and on promoting control and consumerism instead of forging moral and personal obligations. In our analysis, we distinguish two important elements. First, gifts are used to elicit voluntary exposure of personal data by individuals. In exchange for personal data, people are granted material or immaterial rewards. Second, gift relations have a pervasive element of surveillance that aims to influence behavior through p

Ultrasonic force microscopy for nanomechanical characterization of early and late-stage amyloid-β peptide aggregation

The aggregation of amyloid-β peptides into protein fibres is one of the main neuropathological features of Alzheimer’s disease (AD). While imaging of amyloid-β aggregate morphology in vitro is extremely important for understanding AD pathology and development of aggregation inhibitors, unfortunately, potentially highly toxic early aggregates are difficult to observe by current electron microscopy and atomic force microscopy (AFM) methods due to low contrast and variability of peptide attachment to the substrate. Here, we use poly-L-Lysine (PLL) surface that captures all protein components from monomers to fully formed fibres, followed by nanomechanical mapping via Ultrasonic Force Microscopy (UFM), which marries high spatial resolution and nanomechanical contrast with non-destructive nature of tapping mode AFM. For the main putative AD pathogenic component, Aβ1-42, the PLL-UFM approach reveals the morphology of oligomers, protofibrils and mature fibres, and finds that a fraction of small oligomers is still present at later stages of fibril assembly