Nanodiamond-Based Quantum Sensing of Mechano-Regulated Metabolic Plasticity in Cardiac Fibroblasts

Quantum sensors based on single electronic spins, or small spin ensembles in diamonds, can deliver nanoscale spatial resolution in detecting magnetic fields. We have only just started scratching the surface of the application potential of quantum technology in biomedical research and development. Our group has been developing novel nanodiamond-based quantum sensing protocols to investigate mechano-regulation of metabolism at sub-cellular level. In this study, we have focused on the mechano-regulation in the heart scar formation. The myocardial scar formation known as cardiac fibrosis is a key contributor to heart failure. Anti-fibrotic therapies are still under development due to limited understanding of molecular processes behind scar formation. The cardiac fibrosis starts with changes in the mechanical properties of a heart extracellular matrix (ECM), which leads to transdifferentiation of cardiac fibroblasts (quiescent stage) into myofibroblasts (activated stage). We have very little knowledge about how mechanical stimuli govern metabolic plasticity of these cells. Free radicals (FRs), a class of reactive molecules with an unpaired electron, have emerged to be crucial for intracellular signalling. However, as FRs are short lived and difficult to detect with the state-of-the art-methods, therefore their role in cardiac metabolic plasticity remained unknown. In our research, we aimed to reveal the role of FRs in plasticity of cells in response to mechanical stimuli using a quantum sensing technique called T1 relaxometry combined with optical trapping (fluorescent nanodiamonds were used as sensors) and complemented by lipidomics. We have studied how mechanical stimuli influence FR generation, looked at the correlation between FRs level and viscoelastic properties of mitochondria network as well as the lipids profile across the population of cardiac fibroblasts. As a result our research shed light on the mechanobiology of the heart scarring process.