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Single-molecule force spectroscopy reveals signatures of glassy dynamics in the energy landscape of ubiquitin

Nature Physics volume 2, pages 282–286 (2006)Cite this article

Abstract

The conformational energy landscape of a protein out of equilibrium is poorly understood. We use single-molecule force-clamp spectroscopy to measure the kinetics of unfolding of the protein ubiquitin under a constant force. We discover a surprisingly broad distribution of unfolding rates that follows a power law with no characteristic mean. The structural fluctuations that give rise to this distribution reveal the architecture of the protein’s energy landscape. Following models of glassy dynamics, this complex kinetics implies large fluctuations in the energies of the folded protein, characterized by an exponential distribution with a width of 5–10kBT. Our results predict the existence of a ‘glass transition’ force below which the folded conformations interconvert between local minima on multiple timescales. These techniques offer a new tool to further test statistical energy landscape theories experimentally.

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Figure 1: AFM force-clamp spectroscopy experiments on single polyproteins.
Figure 2: Average unfolding trajectory obtained by summing over 416 single-chain trajectories or 2,625 events (black curve), analogous to ensemble measurements.
Figure 3: Normalized histogram of the unfolding rates of each poly-ubiquitin chain.
Figure 4: Histogram in Fig. 3 plotted on a log–log scale reveals a power-law distribution of rate constants (blue diamonds) per ubiquitin chain that spans more than two decades with a decay exponent γ=1.8.
Figure 5: Shape and breadth of the distribution of energy barriers in the protein energy landscape under a constant force.

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Acknowledgements

We would like to thank H. H. Huang for making the ubiquitin construct, S. Garcia-Manyes for data collection, and H. A. Makse and A. J. Tolley for enlightening discussions. This work has been supported by NIH grant R01 HL66030 to J.M.F.

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Authors and Affiliations

  1. Department of Biological Sciences, Columbia University, New York, New York, 10027, USA

    Jasna Brujić, Rodolfo I. Hermans Z., Kirstin A. Walther & Julio M. Fernandez

  2. Department of Applied Physics and Applied Mathematics, Columbia University, New York, New York, 10027, USA

    Rodolfo I. Hermans Z.

  3. Department of Physics, Columbia University, New York, New York, 10027, USA

    Kirstin A. Walther

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Correspondence to Jasna Brujić or Julio M. Fernandez.

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Brujić, J., Hermans Z., R., Walther, K. et al. Single-molecule force spectroscopy reveals signatures of glassy dynamics in the energy landscape of ubiquitin. Nature Phys 2, 282–286 (2006). https://doi.org/10.1038/nphys269

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