Ultrasonic force microscopy for nanomechanical characterization of early and late-stage amyloid-ß peptide aggregation
Article May 11, 2014
Claire Tinker-Mill, Jennifer Mayes, David Allsop, Oleg V. Kolosov
Abstract: The aggregation of amyloid-ß peptides into protein fibres is one of the main neuropathological features of Alzheimer's disease (AD). While imaging of amyloid-ß aggregate morphology in vitro is extremely important for understanding AD pathology and in the 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 a 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 the non-destructive nature of tapping mode AFM. For the main putative AD pathogenic component, Aß1-42, 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.
New Crystal Structure of (Ph)PINK1 Aids Understanding of Early Onset Parkinson’sArticle
Scientists have determined the crystal structure of PhPINK1 bound to it's substrate ubiquitin. Mutations of PINK1 are associated with early onset Parkinson's disease and it is expected that this information will help the design of Parkinson's therapeutics.READ MORE