In this talk, I will introduce “Convex Lens-induced Confinement (CLiC)” imaging, which works by mechanically confining single-molecules to an optical microscope’s field of view, isolating them in nanofabricated features, and eliminates the complexity and potential biases inherent to tethering molecules. I will discuss applications of our single-molecule platform to study structure-mediated DNA interactions in out-of-equilibrium conditions (Shaheen et. al., Nucl. Acid Research 2022), and how CLiC is helping develop emerging classes of genetic medicines by studying their interactions with nucleic acids. Finally, I will highlight current and future applications to connect our observations from single molecule to single cells.
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