Dynamic Force Spectroscopy

Weak-noncovalent interactions govern structural cohesion and mediate most of life’s functions from the outer membrane surface to the interior nucleus of a cell. On laboratory time scales, the energy landscape of a weak bond is fully explored by Brownian-thermal excitations, and energy barriers along its dissociation pathway(s) become encoded in a rate of unbonding that can range from ∼l/μs to 1/year. When pulled apart with a ramps of force, the dissociation kinetics become transformed into a dynamic spectrum of unbonding force as a function of the steepness of the force ramps (loading rates). Expressed on a logarithmic scale in loading rate, the spectrum of breakage forces begins first with a crossover from near equilibrium to far from equilibrium unbonding and then rises through ascending regimes of strength. These regimes expose the prominent energy barriers traversed along the dissociation pathway. Labelled as dynamic force spectroscopy [7,10], this approach is being used to probe the inner world of biomolecular interactions [7, 8, 13, 14, 23, 24, 26, 30] and reveals energy barriers that are difficult or impossible to access by solution assays of near-equilibrium kinetics. These hidden barriers are crucial for specialized dynamic functions of molecules.

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[11]  E. Evans,et al.  Strength of a weak bond connecting flexible polymer chains. , 1999, Biophysical journal.

[12]  Ying-Jie Zhu,et al.  Loading-rate dependence of individual ligand-receptor bond-rupture forces studied by atomic force microscopy , 2001 .

[13]  Helmut Grubmüller,et al.  Force spectroscopy of single biomolecules. , 2002, Chemphyschem : a European journal of chemical physics and physical chemistry.

[14]  T. Beebe,et al.  Specific Interactions between Biotin and Avidin Studied by Atomic Force Microscopy Using the Poisson Statistical Analysis Method , 1999 .

[15]  Evan Evans,et al.  Chemically distinct transition states govern rapid dissociation of single L-selectin bonds under force , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[16]  R. Merkel,et al.  Energy landscapes of receptor–ligand bonds explored with dynamic force spectroscopy , 1999, Nature.

[17]  H. Güntherodt,et al.  Dynamic force spectroscopy of single DNA molecules. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[18]  T. Beebe,et al.  Determination of Single-Bond Forces from Contact Force Variances in Atomic Force Microscopy , 1996 .