Near-Equilibrium Unbinding of Streptavidin-Biotin Using Single-Molecule Acoustic Force Spectroscopy.

Saravanan, Yogesh; Villanueva, Lorenzo; Leveque, Christian; Modesti, Mauro; El Far, Oussama; Valotteau, Claire; Rico, Felix · Nano Lett · 2025

basic_science · Level V

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Abstract

The dissociation of the streptavidin-biotin (SA-b) bond has been widely characterized using bulk and single-molecule force spectroscopy (SMFS) techniques. However, dissociation rates (<i>k</i><sub>off</sub>) from SMFS (∼10<sup>-1</sup> s<sup>-1</sup>) differ from bulk approaches (∼10<sup>-6</sup>-10<sup>-5</sup> s<sup>-1</sup>), likely because SMFS measurements are conducted far from equilibrium. Near-equilibrium SMFS requires high-throughput measurements to obtain large enough statistics and high stability over long periods for ultraslow loading force rates measurements, impractical in most SMFS techniques. Here, we developed <i>in situ</i> force calibration strategies for acoustic force spectroscopy to probe SA-b unbinding forces in the near-equilibrium regime, from 10 down to 10<sup>-3</sup> pN/s. The resulting <i>k</i><sub>off</sub> matches bulk measurements values. Combined with our previous data, we covered 15 orders of magnitude in loading rate, expanding the dynamic range of SMFS and enabling a more complete description of the energy landscape of biomolecular processes.

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