1. Structural Biology and Molecular Biophysics
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Piezo's membrane footprint and its contribution to mechanosensitivity

  1. Christoph A Haselwandter  Is a corresponding author
  2. Roderick MacKinnon  Is a corresponding author
  1. University of Southern California, United States
  2. Howard Hughes Medical Institute, The Rockefeller University, United States
Research Article
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Cite this article as: eLife 2018;7:e41968 doi: 10.7554/eLife.41968

Abstract

Piezo1 is an ion channel that gates open when mechanical force is applied to a cell membrane, thus allowing cells to detect and respond to mechanical stimulation. Molecular structures of Piezo1 reveal a large ion channel with an unusually curved shape. This study analyzes how such a curved ion channel interacts energetically with the cell membrane. Through membrane mechanical calculations, we show that Piezo1 deforms the membrane shape outside the perimeter of the channel into a curved 'membrane footprint'. This membrane footprint amplifies the sensitivity of Piezo1 to changes in membrane tension, rendering it exquisitely responsive. We assert that the shape of the Piezo channel is an elegant example of molecular form evolved to optimize a specific function, in this case tension sensitivity. Furthermore, the predicted influence of the membrane footprint on Piezo gating is consistent with the demonstrated importance of membrane-cytoskeletal attachments to Piezo gating.

Article and author information

Author details

  1. Christoph A Haselwandter

    Department of Physics and Astronomy, University of Southern California, Los Angeles, United States
    For correspondence
    cah77@usc.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5012-5640
  2. Roderick MacKinnon

    Laboratory of Molecular Neurobiology and Biophysics, Howard Hughes Medical Institute, The Rockefeller University, New York, United States
    For correspondence
    mackinn@mail.rockefeller.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7605-4679

Funding

National Science Foundation (DMR-1554716)

  • Christoph A Haselwandter

Howard Hughes Medical Institute

  • Roderick MacKinnon

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Baron Chanda, University of Wisconsin-Madison, United States

Publication history

  1. Received: September 16, 2018
  2. Accepted: November 26, 2018
  3. Accepted Manuscript published: November 27, 2018 (version 1)

Copyright

© 2018, Haselwandter & MacKinnon

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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