Biomolecular and Biological Applications of Solid-State NMR with Dynamic Nuclear Polarization Enhancement

Abstract

Solid-state NMR spectroscopy (ssNMR) with magic-angle spinning (MAS) enables the investigation of biological systems within their native context, such as lipid membranes, viral capsid assemblies, and cells. However, such ambitious investigations often suffer from low sensitivity due to the presence of significant amounts of other molecular species, which reduces the effective concentration of the biomolecule or interaction of interest. Certain investigations requiring the detection of very low concentration species remain unfeasible even with increasing experimental time for signal averaging. By applying dynamic nuclear polarization (DNP) to overcome the sensitivity challenge, the experimental time required can be reduced by orders of magnitude, broadening the feasible scope of applications for biological solid-state NMR. In this review, we outline strategies commonly adopted for biological applications of DNP, indicate ongoing challenges, and present a comprehensive overview of biological investigations where MAS-DNP has led to unique insights.

Highly bioresistant, hydrophilic and rigidly linked trityl-nitroxide biradicals for cellular high-field dynamic nuclear polarization

“…To the best of our knowledge, StaPol-1 represents the first PA that combines excellent performance at high magnetic fields with long-term stability in cellular settings, making it highly attractive for a broad range of cellular DNP-based ssNMR applications. Our present work advances our understanding of TN biradical-based polarizing agents and provides new routes for optimization of high-field polarizing agents for biomolecular applications, 56,57 particularly in bioreductive environments.…”

Optimizing chemistry at the surface of prodrug-loaded cellulose nanofibrils with MAS-DNP

“…Following our recent work, we used Magic Angle Spinning Dynamic Nuclear Polarization (MAS-DNP) to record sensitivity-enhanced solid-state NMR spectra of the functionalized CNF samples. MAS-DNP has recently become a key NMR approach to study with unprecedented sensitivity and thus atomistic details various types of systems from functional material to complex biomolecular systems [37][38][39][40][41] , including cellulosic materials 21,[42][43][44][45][46][47][48] . This approach complements standard ssNMR experiments which are routinely used to characterize nanocellulose but have also been shown to be limited in terms of sensitivity, especially to detect low weight percent chemical modifications on the surface of CNMs 20 .…”

PyrroTriPol: a semi-rigid trityl-nitroxide for high field dynamic nuclear polarization

“…2,4–8 Polarization transfer results in a substantial increase in sensitivity, e.g. with a theoretical enhancement of 1 H ∼ 658 and 13 C ∼ 2633, enabling new insights into structure and function in biology 9–16 and materials. 3–5,17–20…”

“…2,[4][5][6][7][8] Polarization transfer results in a substantial increase in sensitivity, e.g. with a theoretical enhancement of 1 H ∼ 658 and 13 C ∼ 2633, enabling new insights into structure and function in biology [9][10][11][12][13][14][15][16] and materials. [3][4][5][17][18][19][20] Several DNP mechanisms have been proven to be active under MAS at high magnetic eld (>5 T), namely the solid effect (SE), the Overhauser effect (OE) and the cross effect (CE).…”