Islet amyloid polypeptide (IAPP) is a hormone co-secreted with insulin from pancreatic β-cells. Under pathological conditions, IAPP aggregates into cytotoxic oligomers and insoluble amyloid fibrils, impairing β-cell function and potentially contributing to type 2 diabetes (T2D). Although various methods have been developed to screen amyloid inhibitors, many are time-consuming and require specialized equipment. Here, we present a label-free liquid crystal (LC)-based sensing platform for monitoring IAPP aggregation in aqueous solutions. At the LC/aqueous interface where the LC adopts a homeotropic orientation, the formation of IAPP aggregates disrupts the LC ordering, resulting in a distinct dark-to-bright optical transition at concentrations as low as 250 nM. We showed that this transition resulted from the formation of peptide oligomers. By using this mechanism, the system effectively differentiates small molecules with varying inhibitory effects on IAPP aggregation, offering a clear visual readout of changes in LC alignment. This platform thus provides a straightforward and efficient tool for real-time monitoring of peptide aggregation and high-throughput screening of potential anti-amyloid and anti-oligomerization compounds, ultimately facilitating the development of therapeutic strategies against T2D and other amyloid-related disorders.
