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Here we report on the use of double-nanohole (DNH) optical tweezers as alabel-free and free-solution single-molecule probe for protein-DNAinteractions. Using this approach, we demonstrate the unzipping of individual10 base pair DNA-hairpins, and quantify how tumor suppressor p53 protein delaysthe unzipping. From the Arrhenius behavior, we find the energy barrier tounzipping introduced by p53 to be $2\times 10^{-20}$ J, whereas cys135sermutant p53 does not show suppression of unzipping, which gives clues to itsfunctional inability to suppress tumor growth. This transformative approach tosingle molecule analysis allows for ultra-sensitive detection andquantification of protein-DNA interactions to revolutionize the fight againstgenetic diseases.

Nanoplasmonic Tweezers Visualize Protein p53 Suppressing Unzipping of Single DNA-Hairpins