We will present recent results establishing 19 F high-frequency (40–110 kHz) magic angle spinning (MAS) NMR and dynamic nuclear polarization (DNP) approaches that overcome sensitivity and resolution bottlenecks in atomic-level characterization of large biological assemblies, pharmaceutical formulations at natural abundance, and proteins in their natural cellular milieus. We will introduce 19 F DNP-enhanced MAS NMR spectroscopy in protein assemblies and proteins in mammalian cells. We will demonstrate that with very large, over 35-fold signal enhancements afforded by these experiments, high signal-to-noise ratio MAS NMR spectra on nanomole-quantities of proteins in cells can be recorded in only minutes, and two-dimensional dipolar correlation spectra with remarkable resolution are obtained. This work paves the way for 19 F DNP-enhanced MAS NMR applications in cellular milieus, for probing protein structure, dynamics and ligand interactions in native-like environments.
Polenova et al. (2026) studied this question.