The ability to measure the dynamics of biological processes at the single-molecule level is essential to unraveling complex living systems. In processes such as enzymatic unwinding of DNA, the displacements of the involved molecules are subtle in comparison with their rotation and thus the dynamics can be more robustly and precisely measured by tracking the rotational movement. In this project, we will advance the microscopy based on polarization-resolved interferometric detection of scattered light to enable rotational tracking of a molecule either unlabeled or with a rotation label based on DNA origami and plasmonic nanoparticle. The unique combination of the sensitive interferometric detection and truly nanoscale scattering labels will yield unprecedented µs-level temporal resolution enabling observation of the fastest DNA-processing enzymes at close-to-physiological conditions. Furthermore, the measurement of rotational diffusion to determine the conformational or folding dynamics of unlabeled freely diffusing molecules confined within nanofluidic channels will be assessed.
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