MAS cryoprobe enhances solid-state NMR signals of α-synuclein fibrils

Abstract

Solid-state NMR spectroscopy is increasingly applied to structural and dynamics studies across a broad range of chemical, material, and biological systems. Although sensitivity has traditionally been a major limitation, the recently developed MAS cryoprobe has been shown to substantially overcome this challenge. Its ability to enhance the signal-to-noise (S/N) ratio without requiring sample freezing makes it particularly attractive for investigating non-isotropic systems, including soft materials (e.g., hydrogels), semi-solids (e.g., membrane mimetics) and rigid solids (e.g., amyloid fibrils). In this study, we report on the enhanced sensitivity of solid-state NMR experiments on -synuclein fibrils using a MAS cryoprobe. Nearly an order-of-magnitude improvement in S/N was observed in CPMAS, refocused-INEPT and 2D 13C-13C chemical shift correlation spectra of -synuclein fibrils compared with data collected on a conventional MAS probe. The improved S/N enables the acquisition of slowly decaying signals in the indirect dimension, facilitating faster, high-resolution multidimensional solid-state NMR spectroscopy. We therefore anticipate that MAS cryoprobe will become increasingly valuable for structural studies a wide range of samples that are less abundant, less stable, or transient, such as amyloid intermediates.