Counting and Breaking Single Bonds

Dynamic Force Spectroscopy in Tethered Single Molecule Systems
  • Todd A. Sulchek
  • Raymond W. Friddle
  • Aleksandr Noy

Tethered molecular systems, in which flexible polymer linkers connect the interacting molecules to the surfaces of the atomic force microscope probe and target sample, provide a particularly attractive platform for studying biological interactions using force spectroscopy. We describe the underlying nanomechanics of individual tether molecules. We provide a sampling from the literature that illustrates how knowledge and control of tether linkage can aid understanding of molecular interactions. We then describe the basic physical principles of force spectroscopy measurements of tethered biological interactions and show that well-defined mechanical properties of the tether linkages allow independent determination of the number of ruptured bonds. This approach allows us to show that forces between multiple biological bonds measured in a parallel configuration obey the predictions of a Markovian model of bond dissociation. Finally, we discuss the use of the dynamic force spectra of single and multiple protein-ligand bonds for determination of kinetic parameters for multivalent interactions. This ability to form, count, and dissociate biological bonds with nanomechanical forces provides a powerful method to study the physical laws governing the interactions of biological molecules.


Contour Length Bond Rupture Force Spectroscopy Rupture Force Tethered System 
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Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Todd A. Sulchek
    • 1
  • Raymond W. Friddle
    • 2
  • Aleksandr Noy
    • 3
  1. 1.Chemistry, Materials and Life Sciences DirectorateLawrence Livermore National Laboratory, L-231LivermoreUSA
  2. 2.Chemistry, Materials and Life Sciences DirectorateLawrence Livermore National Laboratory, L-234LivermoreUSA
  3. 3.Chemistry, Materials and Life Sciences DirectorateLawrence Livermore National Laboratory, L-234LivermoreUSA

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