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

TL;DR

This study employs nanoplasmonic optical tweezers to visualize how tumor suppressor p53 protein delays DNA hairpin unzipping, providing insights into protein-DNA interactions relevant to cancer suppression.

Contribution

It introduces a label-free, free-solution single-molecule technique using double-nanohole optical tweezers to study protein-DNA interactions with high sensitivity.

Findings

p53 delays DNA hairpin unzipping

Energy barrier to unzipping increased by p53

Mutant p53 does not suppress unzipping

Abstract

Here we report on the use of double-nanohole (DNH) optical tweezers as a label-free and free-solution single-molecule probe for protein-DNA interactions. Using this approach, we demonstrate the unzipping of individual 10 base pair DNA-hairpins, and quantify how tumor suppressor p53 protein delays the unzipping. From the Arrhenius behavior, we find the energy barrier to unzipping introduced by p53 to be $2\times 10^{-20}$ J, whereas cys135ser mutant p53 does not show suppression of unzipping, which gives clues to its functional inability to suppress tumor growth. This transformative approach to single molecule analysis allows for ultra-sensitive detection and quantification of protein-DNA interactions to revolutionize the fight against genetic diseases.