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Friday, February 2, 2018

Single-Molecule Mechanochemical pH Sensing Revealing the Proximity Effect of Hydroniums Generated by an Alkaline Phosphatase

Prakash Shrestha, Yunxi Cui, Jia Wei, Sagun Jonchhe, and Hanbin Mao

Due to the fast diffusion, small molecules such as hydronium ions (H3O+) are expected to be homogeneously distributed, even close to the site-of-origin. Given the importance of H3O+ in numerous processes, it is surprising that H3O+ concentration ([H3O+]) has yet to be profiled near its generation site with nanometer resolution. Here, we innovated a single-molecule method to probe [H3O+] in nanometer proximity of individual alkaline phosphatases. We designed a mechanophore with cytosine (C)–C mismatch pairs in a DNA hairpin. Binding of H3O+ to these C–C pairs changes mechanical properties, such as stability and transition distance, of the mechanophore. These changes are recorded in optical tweezers and analyzed in a multivariate fashion to reduce the stochastic noise of individual mechanophores. With this method, we found [H3O+] increases in the nanometer vicinity of an active alkaline phosphatase, which supports that the proximity effect is the cause for increased rates in cascade enzymatic reactions.

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