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A Membrane Thickness Sensor in TREK-1 Channels Transduces Mechanical Force

40 Pages Posted: 8 Apr 2018 Publication Status: Review Complete

See all articles by Arman Nayebosadri

Arman Nayebosadri

The Scripps Research Institute - Department of Molecular Therapeutics

E. Nicolas Petersen

The Scripps Research Institute - Department of Molecular Therapeutics; The Scripps Research Institute - Scripps Graduate Program

Cerrone Cabanos

The Scripps Research Institute - Department of Molecular Therapeutics

Scott B. Hansen

The Scripps Research Institute - Department of Molecular Therapeutics

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Abstract

The transduction of force to a biological signal is critical to all living organisms and cells. Mechanosensitive ion channels participate, but the biophysical mechanism that transduces force remains unclear. Here we show that the sensing of membrane thinning through a helix tilt in TREK-1 channels transduces force. Reconstituted TREK-1 in PC lipids with a hydrophobic thickness of ~29 Å (18:1 PC) robustly activated the channel; however, decreasing the thickness to ~26 Å (16:1 PC) or increasing to ~36 Å (22:1 PC) inhibited the channel. Increasing bilayer thickness by adding cholesterol (10-40%), or thinning the membrane with stretch, polyunsaturated fatty acids, or heat shifted the thickness dependence. The thickness sensitivity was located near a lipid-binding motif on a known gating helix at the end of the fourth transmembrane domain. We propose a stretch-activation model for TREK-1 where tension causes membrane thinning and TREK-1 senses membrane thinning to transduce the signal.

Suggested Citation

Nayebosadri, Arman and Petersen, E. Nicolas and Cabanos, Cerrone and Hansen, Scott B., A Membrane Thickness Sensor in TREK-1 Channels Transduces Mechanical Force (2018). Available at SSRN: https://ssrn.com/abstract=3155650 or http://dx.doi.org/10.2139/ssrn.3155650
This version of the paper has not been formally peer reviewed.

Arman Nayebosadri

The Scripps Research Institute - Department of Molecular Therapeutics

130 Scripps Way
Jupitor, FL
United States

E. Nicolas Petersen

The Scripps Research Institute - Department of Molecular Therapeutics

130 Scripps Way
Jupitor, FL
United States

The Scripps Research Institute - Scripps Graduate Program

130 Scripps Way
Jupitor, FL
United States

Cerrone Cabanos

The Scripps Research Institute - Department of Molecular Therapeutics

130 Scripps Way
Jupitor, FL
United States

Scott B. Hansen (Contact Author)

The Scripps Research Institute - Department of Molecular Therapeutics ( email )

130 Scripps Way
Jupitor, FL
United States

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