Dynamics of breaking intermolecular bonds in high-speed force spectroscopy

Abstract

Atomic force microscope based single-molecule force spectroscopy provides a description of a variety of intermolecular interactions such as those occurring between receptor molecules and their ligands. Advances in force spectroscopy have enabled performing measurements at high-speeds and sub-microsecond resolutions. We report experiments performed on a biotin-avidin system that reveal that the measured force decreases with the loading rate at high rates. This result is at odds with the established Bell-Evans theory that predicts a monotonic increase of the rupture force with the loading rate. We demonstrate that inertial and hydrodynamic forces generated during the breaking of the bond dominate the measured force at high loading rates. We develop a correction factor to incorporate those effects into the Bell-Evans theory. The correction is necessary to obtain accurate values of the intermolecular forces at high speeds.

Molecular Recognition by Silicon Nanowire Field-Effect Transistor and Single-Molecule Force Spectroscopy

“…Figure 6a shows the overall distribution of force values. The average measured force, F m * = 60.8 pN, agreed well with reported data obtained with cantilevers of similar stiffness [34,40].…”

“…All force-displacement curves were transformed into force-distance curves by d = z + F/k. To detect the specific unbinding events, a custom written code was used (MATLAB, MathWorks, Natick, MA, USA) [34]. It fitted the retraction part of the SMFS curves with a polynomial function of grade 7.…”

Nanomechanical mapping of soft materials with the atomic force microscope: methods, theory and applications

“…However, performing a FV experiment at highspeeds (say 1 frame per s) requires a rigorous analysis of the transformation of a deflection into a force value. 27,125 The equation of motion that describes force-volume (eqn (3)) shows the tip-surface F ts expressed in terms of the cantilever restoring force, an inertial term and a hydrodynamic force associated with the interaction of the cantilever with the fluid. To illustrate explicitly the dependence of the force on the modulation frequency, let's introduce a normalized time variable t = ot…”

Concurrent atomic force spectroscopy

“…For example, unpredictable changes in k sc during experimentation due to instrument drift, material accumulation, or mechanical wear of the cantilever would, on average, affect measurements of the proteins in the sample equally. Indeed, we propose that concurrent atomic force spectroscopy strategies, in combination with available theoretical and experimental developments addressing other limitations of the AFM such as deviations from non-ideal pulling geometry 35 , can be key to exploit the advantages of next-generation cantilevers, which are pushing the AFM into ranges of force, speed, stability, and time resolution at the expense of more challenging force calibration 14,[36][37][38][39][40] .…”