Quantum sensor-enabled nanoscale magnetic resonance

Magnetic resonance experiments are an indispensable tool in biophysics, providing detailed chemical insight and accessing unique degrees of freedom. However, these methods have poor sensitivity compared to fluorescence techniques, requiring low temperatures and/or concentrated sample conditions, which presents a roadblock to their wider utilization. The long-term goal of this project is to develop novel quantum sensor- enhanced magnetic resonance techniques which can reach the single-molecule regime, with the specific applications to electron transport in metalloproteins and nanoscale motion in membranes. The objective of this proposal is to develop novel strategies for integrating these quantum sensors (the NV center in diamond) with proteins and biomembranes. Our innovation is a suite of experimental strategies to improve the sensor compatibility with biological systems, ranging from minimizing photodamage using a total internal reflection geometry, to localizing targets at the sensor surface with supported lipid bilayer formation. Our rationale for this overall approach is that NV centers have found extensive applications in condensed matter physics and materials science because of their outstanding performance as magnetic resonance sensors, yet progress in biophysical contexts has been much slower because of the more demanding nature of the biological samples. Addressing these challenges would allow us to leverage the uniquely-powerful properties of the NV center – picotesla sensitivity, fluorescence readout, single-spin detection – to enhance the capabilities of magnetic resonance (NMR, ESR) techniques. The first research direction this new tool will enable is probing electron transfer in metalloproteins; we will be able to, at room temperature, probe the Fe-heme spin in cyctochrome c (and related proteins) to access spin and conformational information, while also probing time-dependent behavior to extract electron transfer rates. Our hypothesis here is that the complex spin-state behavior of Fe ions (e.g., admixture states first identified in the 1970s) is a functionally-important factor in electron transport, and which will be required to explain a range of novel behaviors in heme protein superstructures, such as metallic conduction and spin-dependent transport. Our second research direction focuses on probing diffusion on the <10nm length scale, beyond the limits of even most super-resolution techniques. Our hypothesis here is that nanoscopic domain formation (which we will induce with multicomponent lipid compositions) will introduce significant deviations from Brownian diffusion, and that experimentally measuring this will provide new insight into motion in confined environments in cell membranes. This research is significant because improved sensitivity in magnetic resonance experiments would enable transformative new research across multiple fields, and the specific areas we identify here will address long-standing, fundamental biophysical questions. This research will have a positive impact because the new tool we will develop can be broadly applied by other groups, and the new insight we develop will enable broadly applicable mechanistic principles to be articulated. Project Number: 1R35GM160564-01 | Fiscal Year: 2025 | NIH Institute/Center: National Institute of General Medical Sciences (NIGMS) | Principal Investigator: Paul Stevenson | Institution: NORTHEASTERN UNIVERSITY, BOSTON, MA | Award Amount: $394,000 | Activity Code: R35 | Study Section: Special Emphasis Panel[ZRG1 MCST-Q (55)] View on NIH RePORTER: https://reporter.nih.gov/project-details/11203456