Solid-state dynamic nuclear polarization (ssDNP) is an NMR signal-enhancing technique by on-resonant microwave (MW) irradiation of tailored radical-based DNP agents that is attracting dramatic attention in recent years, given its potential to transform the capability of NMR spectroscopy for structural biology as we know it, in particular of solid-state magic angle spinning (MAS) NMR studies of biological solid samples. The potential of ssDNP stems from the ability of this technique to enhance spin polarization by O(102-103) fold. This signal gain, combined with a thermal polarization gain of O(101) fold from cooling to liquid nitrogen temperatures and O(102) from cooling to liquid helium temperatures, together with high magnetic fields, offers a total signal gain of up to O(105) for ssNMR, and accordingly a reduction in experimental time by up to the square of this signal gain. Such dramatic magnitudes of signal enhancement enable unprecedented ssNMR studies of the types of samples and conditions that have been inaccessible to NMR based structure studies before. Among the ssDNP-enabled research highlights are the study of membrane protein systems in whole cells or the study of inter-strand structure determination of the quaternary structure of amyloid fibrils. A particular focus of our development is to enable transient structure studies of aggregating proteins by ssDNP-enhanced MAS NMR of freeze-quenched proteins at various stages of aggregation. In the well-recognized role of ssDNP to enhance MAS NMR as an ultimate high- resolution structural biology tool to capture transiently evolving structures, we propose to address major technological challenges with our innovative instrument developments. The core of our development will be a compact and versatile quasi-optical MW bridge design with novel two-frequency pump, concurrent DNP and EPR, as well as ELDOR capabilities under MAS operation. While, ssDNP-enhanced MAS NMR is the center of focus of contemporary NMR as it has the potential to transform MAS NMR structure studies of biosolids, only a handful of alternative ssDNP MAS NMR instruments exists in the world to the commercial gyrotron-powered ssDNP MAS NMR instrument operating at >100 Kelvin?our instrumental platform for DNP-enhanced MAS NMR aims to offer an alternative solution with greater versatility and performance.
We pursue to develop a modular magic angle spinning (MAS) capable dynamic nuclear polarization (DNP) instrument operating at liquid helium temperatures that exploits the versatility of a broadly frequency tunable solid-state microwave source and quasi optics transmission system to precisely manipulate the microwave transmission to the sample for the purpose of dramatically enhancing the sensitivity for MAS-NMR based structure studies of biological solids. The massive improvement in NMR signal from enhanced DNP performance will enable previously inaccessible MAS-NMR experiments, such as elucidating the structural changes underlying, and driving, protein aggregation?a hallmark of Alzheimer?s disease.
| Lund, Alicia; Equbal, Asif; Han, Songi (2018) Tuning nuclear depolarization under MAS by electron T1e. Phys Chem Chem Phys 20:23976-23987 |
| Leavesley, Alisa; Shimon, Daphna; Siaw, Ting Ann et al. (2017) Effect of electron spectral diffusion on static dynamic nuclear polarization at 7 Tesla. Phys Chem Chem Phys 19:3596-3605 |
| Kaminker, Ilia; Barnes, Ryan; Han, Songi (2017) Arbitrary waveform modulated pulse EPR at 200GHz. J Magn Reson 279:81-90 |
| Eschmann, Neil A; Georgieva, Elka R; Ganguly, Pritam et al. (2017) Signature of an aggregation-prone conformation of tau. Sci Rep 7:44739 |
| Siaw, Ting Ann; Leavesley, Alisa; Lund, Alicia et al. (2016) A versatile and modular quasi optics-based 200GHz dual dynamic nuclear polarization and electron paramagnetic resonance instrument. J Magn Reson 264:131-153 |
