Nanoscale Imaging of α-Synuclein-Induced Membrane Disruption in SH-SY5Y Neuroblastoma Cells Using Scanning Ion Conductance Microscopy
The misfolding and aggregation of α-synuclein (α-Syn) are central to Parkinson’s disease pathology, yet the mechanisms by which α-Syn aggregates disrupt cell membranes remain unclear. In this study, we used scanning ion conductance microscopy (SICM), a non-invasive, label-free imaging technique, to examine how α-Syn oligomers and preformed fibrils (PFFs) alter the membrane morphology of SH-SY5Y neuroblastoma cells. Live-cell SICM imaging showed that oligomers induce pronounced membrane roughening, micrometer-scale deformations, and transient pore formation at higher concentrations, suggesting direct membrane permeabilization. SICM imaging of PFF-treated samples revealed increased membrane roughness and crystalline-like protrusions, with minimal cell death over 48 hours. These results demonstrate distinct membrane interactions for α-Syn oligomers and fibrils and underscore SICM’s utility for nanoscale imaging of neurodegenerative processes.