Lipid vesicles trigger α-synuclein aggregation by stimulating primary nucleation.

α-Synuclein (α-syn) is a 140-residue intrinsically disordered protein that is involved in neuronal and synaptic vesicle plasticity, but its aggregation to form amyloid fibrils is the hallmark of Parkinson's disease (PD). The interaction between α-syn and lipid surfaces is believed to be a key feature for mediation of its normal function, but under other circumstances it is able to modulate amyloid fibril formation. Using a combination of experimental and theoretical approaches, we identify the mechanism through which facile aggregation of α-syn is induced under conditions where it binds a lipid bilayer, and we show that the rate of primary nucleation can be enhanced by three orders of magnitude or more under such conditions. These results reveal the key role that membrane interactions can have in triggering conversion of α-syn from its soluble state to the aggregated state that is associated with neurodegeneration and to its associated disease states.This work was supported by the UK BBSRC and the Wellcome Trust (CMD, TPJK, MV), the Frances and Augustus Newman Foundation (TPJK), Magdalene College, Cambridge (AKB) , St John’s College, Cambridge (TCTM), the Cambridge Home and EU Scholarship Scheme (GM), Elan Pharmaceuticals (CMD, TPJK, MV, CG) and the Leverhulme Trust (AKB).This is the accepted manuscript. The final version is available from NPG at http://www.nature.com/nchembio/journal/v11/n3/abs/nchembio.1750.htm

Characterization, Deposition Mechanisms and Modeling of Metallic Glass Powders for Cold Spray

This chapter describes recent efforts to understand the effects that chemical and physical properties of metallic glass (MG) powder particles have on the synthesis of their cold-sprayed coatings. Understanding the mechanical response of MG is fundamental to evaluate the conditions at which their powder particles can be deposited by cold spray. The characteristics of the feedstock powders are evaluated and used to ascertain ideal cold spray parameters. This information is also used to model the deposition mechanism of metallic glasses in the cold spray process. FE analysis and simulation is used to identify the phenomena behind the formation of MG coatings (i.e., homogenous or inhomogeneous deformation). The model defined considers strain rate and temperature dependence of MGs under different conditions