Ultrastiff Amyloid-Fibril Network of α-Synuclein Formed by Surface Seeding Reaction Confirmed by Multichannel...

We developed a multichannel wireless quartz-crystal-microbalance (QCM) biosensor for mechanically studying the on-surface aggregation reaction of α-synuclein (α-syn). We find a quite unusual change in the resonant frequency that eventually exceeds the baseline, which has never been observed during seeding aggregation reaction. By incorporating a growth-to-percolation theory for fibril elongation reaction, we have favorably reproduced this unusual response and found that it can be explained only with formation of an ultrastiff fibril network. We also find that the stiffness of the fibril network grown from artificially prepared twist-type seeds is significantly higher than that from rod-type seeds. Furthermore, the stiffnesses of fibril networks grown from seeds derived from brain tissues of Parkinson's disease (PD) and multiple system atrophy (MSA) patients show a very similar trend to those of rod and twist seeds, respectively, indicating that fibrils from MSA patients are stiffer than those from PD.