How Does Shear Affect Aβ Fibrillogenesis?

The fibrillogenesis of A beta(1-40) proceeds via three main stages: (i) formation of aggregates from monomers, (ii) linear association of these aggregates to form beaded protofibrils, and (iii) fusion and structural reorganization of protofibrils into mature fibrils. We have studied the effect of shear on the rate of each of these steps through a combination of fluorescence, atomic force microscopy, and circular dichroism experiments. We find that shear increases the rate of the first two stages (aggregation and protofibril formation) and inhibits the third. Our hypothesis is that in the first stage shear mechanically perturbs the peptide from its native state inducing aggregation via hydrophobic interactions; in the second stage, shear enhances the linear alignment of aggregates due to minimization of drag in the shear flow field; in the third stage, exposure to constant and uniform shear inhibits the formation of mature fibrils.