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Force-induced conformational changes in PIEZO1.

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  • 1Department of Anesthesiology, Weill Cornell Medicine, New York, NY, USA.

Nature
|August 23, 2019
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Summary
This summary is machine-generated.

The mechanosensitive channel PIEZO1, a protein converting force into electrical signals, can reversibly flatten into the cell membrane plane. This shape change is key to how PIEZO1 responds to mechanical forces.

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Area of Science:

  • Biophysics
  • Molecular Biology
  • Cell Biology

Background:

  • PIEZO1 is a mechanosensitive ion channel crucial for converting mechanical forces into cellular signals.
  • Previous studies revealed PIEZO1's bowl-shaped trimeric structure with extended arms.

Purpose of the Study:

  • To investigate the structural dynamics of PIEZO1 under varying mechanical conditions.
  • To elucidate the mechanism by which PIEZO1 responds to membrane tension and force.

Main Methods:

  • Cryo-electron microscopy (cryo-EM) was used to observe PIEZO1 structure in lipid vesicles of different sizes.
  • High-speed atomic force microscopy (HS-AFM) analyzed PIEZO1 deformability on mica-supported membranes.
  • Mechanical force was applied to estimate PIEZO1's spring constant.

Main Results:

  • PIEZO1 exhibits varying degrees of curvature depending on lipid vesicle size.
  • PIEZO1 can reversibly flatten into the membrane plane when subjected to force.
  • The mechanical spring constant of PIEZO1 was estimated using force measurements.

Conclusions:

  • PIEZO1's ability to deform its shape, particularly flattening into a planar structure, is demonstrated.
  • This conformational flexibility likely underlies the conversion of lateral membrane tension into free energy changes for channel gating.
  • The findings provide insights into the molecular mechanisms of mechanotransduction by PIEZO1.