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Spatiotemporal relationships defining the adaptive gating of the bacterial mechanosensitive channel MscS

European Biophysics Journal volume 47, pages 663–677 (2018)Cite this article

Abstract

Adaptive desensitization and inactivation are common properties of most ion channels and receptors. The mechanosensitive channel of small conductance MscS, which serves as a low-threshold osmolyte release valve in most bacteria, inactivates not from the open, but from the resting state under moderate tensions. This mechanism enables the channel to respond differently to slow tension ramps versus abruptly applied stimuli. In this work, we present a reconstruction of the energy landscape for MscS transitions based on patch current kinetics recorded under special pressure protocols. The data are analyzed with a three-state continuous time Markov model, where the tension-dependent transition rates are governed by Arrhenius-type relations. The analysis provides assignments to the intrinsic opening, closing, inactivation, and recovery rates as well as their tension dependencies. These parameters, which define the spatial (areal) distances between the energy wells and the positions of barriers, describe the tension-dependent distribution of the channel population between the three states and predict the experimentally observed dynamic pulse and ramp responses. Our solution also provides an analytic expression for the area of the inactivated state in terms of two experimentally accessible parameters: the tension at which inactivation probability is maximized, γ*, and the midpoint tension for activation, γ0.5. The analysis initially performed on Escherichia coli MscS shows its applicability to the recently characterized MscS homolog from Pseudomonas aeruginosa. Inactivation appears to be a common property of low-threshold MscS channels, which mediate proper termination of the osmotic permeability response and contribute to the environmental fitness of bacteria.

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Acknowledgements

We would like to thank the reviewers for their detailed comments and suggestions for the manuscript. The work was supported by NIH R21AI105655 and RO1 GM107652 Grants to SS. UC was supported by the U.S. Department of Education GAANN “Mathematics in Biology” Scholarship. UC is also indebted to Drs. Oren Raz (Weizmann Institute of Science) and Yiğit Subaşı (Los Alamos National Laboratory) for their stimulating discussions. The authors thank Ms. Stephanie Sansbury for cloning MscS into a tightly-regulated pBAD expression system and Madolyn Britt for editorial comments.

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Authors and Affiliations

  1. Institute for Physical Science and Technology, University of Maryland, College Park, MD, 20742, USA

    Uğur Çetiner & Sergei Sukharev

  2. Maryland Biophysics Program, University of Maryland, College Park, MD, 20742, USA

    Uğur Çetiner & Sergei Sukharev

  3. Department of Biology, University of Maryland, College Park, MD, 20742, USA

    Uğur Çetiner, Andriy Anishkin & Sergei Sukharev

Authors
  1. Uğur Çetiner
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  2. Andriy Anishkin
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  3. Sergei Sukharev
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Contributions

UC developed the theoretical formalism, designed and performed the experiments. AA designed the structural models of MscS and analyzed the lateral expansion area. UC, AA and SS wrote the manuscript.

Corresponding authors

Correspondence to Uğur Çetiner or Sergei Sukharev.

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Çetiner, U., Anishkin, A. & Sukharev, S. Spatiotemporal relationships defining the adaptive gating of the bacterial mechanosensitive channel MscS. Eur Biophys J 47, 663–677 (2018). https://doi.org/10.1007/s00249-018-1303-5

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  • DOI: https://doi.org/10.1007/s00249-018-1303-5

Keywords

  • MscS
  • Osmotic fitness
  • Markov chains
  • Energy landscape