Loading-Rate Dependence of Individual Ligand−Receptor Bond-Rupture Forces Studied by Atomic Force Microscopy

Abstract

It is known that bond strength is a dynamic property that is dependent upon the force loading rate applied during the rupturing of a bond. For biotin−avidin and biotin−streptavidin systems, dynamic force spectra, which are plots of bond strength vs loge(loading rate), have been acquired in a recent biomembrane force probe (BFP) study1 at force loading rates in the range 0.05−60 000 pN/s. In the present study, the dynamic force spectrum of the biotin−streptavidin bond strength in solution was extended from loading rates of ∼104 to ∼107 pN/s with the atomic force microscope (AFM). A Poisson statistical analysis method was applied to extract the magnitude of individual bond-rupture forces and nonspecific interactions from the AFM force−distance curve measurements. The bond strengths were found to scale linearly with the logarithm of the loading rate. The nonspecific interactions also exhibited a linear dependence on the logarithm of loading rate, although not increasing as rapidly as the specific interactions. The dynamic force spectra acquired here with the AFM combined well with BFP measurements by Merkel et al. The combined spectrum exhibited two linear regimes, consistent with the view that multiple energy barriers are present along the unbinding coordinate of the biotin−streptavidin complex. This study demonstrated that unbinding forces measured by different techniques are in agreement and can be used together to obtain a dynamic force spectrum covering 9 orders of magnitude in loading rate.

Force measurements with the atomic force microscope: Technique, interpretation and applications

“…The dependence of the bond-rupture force on the loading/unloading rate has been studied in a number of works [673,1132,1133]. Lo et al [1134] have studied this dependence with biotin-streptavidin, taking advantage of the Poisson statistic method illustrated in Section 5, and have shown that the bond strength depends linearly on the logarithm of the loading rate (see Eq. (11.5)).…”

Single cell profiling of surface carbohydrates on Bacillus cereus

“…The high level of control of scan size, scan speed and loading as reported in this paper results in an accurate estimation of surface composition. In these experiments, a ramp velocity of 0.9 mm s 21 was used, which reduces time of experiment while minimizing the effect of hydrodynamic drag force and hysteresis [55,56]. One complete force map on an area of approximately 4 Â 4 mm with a resolution of 80 Â 80 (6400 force curves) can be easily obtained in less than 1 h without drift, tip damage or multiple interactions.…”

A nanomechanical interface to rapid single-molecule interactions

“…The loading rate dependency of most likely rupture forces contains information about the energy landscape of receptor-ligand interactions. When measured over a wide dynamic range and plotted on a logarithmic scale, different energy barriers can be resolved from the changes in the slope 15,24,25 . The position of the barrier x β is related to the slope f β by f β = k B T/x β (here k B is Boltzmann constant and T is temperature) 24,26 .…”