Scanning ion conductance microscopy studies of amyloid fibrils at nanoscale

Atomic force microscopy (AFM) has developed to become a very versatile nano-scale technique to reveal the three-dimensional (3D) morphology of amyloid aggregates under physiological conditions. However, the imaging principle of AFM is based on measuring the 'force' between a sharp tip and a given nanostructure, which may cause mechanical deformation of relatively soft objects. To avoid the deformation, scanning ion conductance microscopy (SICM) is an alternative scanning probe microscopy technique, operating with alternating current mode. Here we can indeed reveal the 3D morphology of amyloid fibrils and it is capable of exploring proteins with nanoscale resolution. Compared with conventional AFM, we show that SICM can provide precise height measurements of amyloid protein aggregates, a feature that enables us to obtain unique insight into the detailed nucleation and growth mechanisms behind amyloid self-assembly.