Tension-dependent structural deformation alters single-molecule transition kinetics

• DOI: 10.1073/pnas.1010047108
• Publication Date: 2011-01-19T05:04:46Z
• Authors: B. Sudhanshu; S. Mihardja; E. F. Koslover; S. Mehraeen; C. Bustamante; A. J. Spakowitz
• Keywords: Kinetics; 0303 health sciences; 03 medical and health sciences; Molecular Structure; Biophysics; Models, Theoretical; Nucleosomes

We analyze the response of a single nucleosome to tension, which serves as a prototypical biophysical measurement where tension-dependent deformation alters transition kinetics. We develop a statistical-mechanics model of a nucleosome as a wormlike chain bound to a spool, incorporating fluctuations in the number of bases bound, the spool orientation, and the conformations of the unbound polymer segments. With the resulting free-energy surface, we perform dynamic simulations that permit a direct comparison with experiments. This simple approach demonstrates that the experimentally observed structural states at nonzero tension are a consequence of the tension and that these tension-induced states cease to exist at zero tension. The transitions between states exhibit substantial deformation of the unbound polymer segments. The associated deformation energy increases with tension; thus, the application of tension alters the kinetics due to tension-induced deformation of the transition states. This mechanism would arise in any system where the tether molecule is deformed in the transition state under the influence of tension.