High-Speed Force Spectroscopy Unbinds Streptavidin-Biotin at the Velocity of Molecular Dynamics Simulations

Abstract

The forced disruption of the (strept)avidin-biotin complex by atomic force microscopy (AFM) and other techniques opened the field and established the basis of single molecule force spectroscopy (1-3). Steered molecular dynamics (SMD) simulations provided atomic description of the unbinding process (4). However, the maximum experimental AFM velocities were typically of 10 µm/s, while SMD simulations were performed in the range of 1 m/s to 10 m/s. Recent development of high-speed force spectroscopy (HS-FS) using HS-AFM allowed velocities in the mm/s range (5). We have applied HS-FS to probe the binding strength of the streptavidin-biotin complex at velocities up to ∼8 mm/s, paralleled by SMD simulations. The experimental dynamic force spectrum of the unbinding process is compared with SMD simulations. The combination of HS-FS and SMD at overlapping velocities provides an atomic description of the unbinding process measured by experiment.1. Merkel, R., P. Nassoy, A. Leung, K. Ritchie, and E. Evans. 1999. Energy landscapes of receptor-ligand bonds explored with dynamic force spectroscopy. Nature 397:50-53.2. Florin, E. L., V. T. Moy, and H. E. Gaub. 1994. Adhesion Forces Between Individual Ligand-Receptor Pairs. Science 264:415-417.3. Lee, G. U., D. A. Kidwell, and R. J. Colton. 1994. Sensing Discrete Streptavidin Biotin Interactions with Atomic-Force Microscopy. Langmuir 10:354-357.4. Grubmuller, H., B. Heymann, and P. Tavan. 1996. Ligand binding: Molecular mechanics calculation of the streptavidin biotin rupture force. Science 271:997-999.5. Rico, F., L. Gonzalez, I. Casuso, M. Puig-Vidal, and S. Scheuring. 2013. High-Speed Force Spectroscopy Unfolds Titin at the Velocity of Molecular Dynamics Simulations. Science 342:741-743.