Piezo1 Channels are Inherently Mechanosensitive

Abstract

The conversion of mechanical force to chemical signals is critical for many biological processes, including the sense of touch, pain, and hearing. Mechanosensitive ion channels play a key role in sensing the mechanical stimuli experienced by various cell types, and are present in bacteria to mammals. Bacterial mechanosensitive channels are characterized thoroughly, but less is known about their counterparts in vertebrates. Piezos have been recently established as ion channels required for mechanotransduction in disparate cell types in vitro and in vivo. Overexpression of Piezos in heterologous cells gives rise to large mechanically activated currents; however, it is unclear whether Piezos are inherently mechanosensitive or rely on alternate cellular components to sense mechanical stimuli. Here we show that mechanical perturbations of the lipid bilayer alone are sufficient to activate Piezo channels, illustrating their innate ability as molecular force transducers. eTOCCorrespondence and requests for materials should be addressed to R.S. (ruhma@scripps.edu). * Lead Contact: Ruhma Syeda (ruhma@scripps.edu) Author Contributions R.S and A.P. designed the experiments, and wrote the manuscript. R.S, M.F, J.K conducted Piezo1 purification with the help from J.S. R.S conducted electrical recordings and performed analysis. C.D.C. and B.M. provided MscS protein, analyzed bilayer tension data and wrote the manuscript.Author Information: The authors declare no competing interests.Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. HHS Public Access