Piezo1 ion channels inherently function as independent mechanotransducers

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Abstract

<jats:p>Piezo1 is a mechanically activated ion channel involved in sensing forces in various cell types and tissues. Cryo-electron microscopy has revealed that the Piezo1 structure is bowl-shaped and capable of inducing membrane curvature via its extended footprint, which indirectly suggests that Piezo1 ion channels may bias each other’s spatial distribution and interact functionally. Here, we use cell-attached patch-clamp electrophysiology and pressure-clamp stimulation to functionally examine large numbers of membrane patches from cells expressing Piezo1 endogenously at low levels and cells overexpressing Piezo1 at high levels. Our data, together with stochastic simulations of Piezo1 spatial distributions, show that both at endogenous densities (1–2 channels/μm<jats:sup>2</jats:sup>), and at non-physiological densities (10–100 channels/μm<jats:sup>2</jats:sup>) predicted to cause substantial footprint overlap, Piezo1 density has no effect on its pressure sensitivity or open probability in the nominal absence of membrane tension. The results suggest that Piezo channels, at densities likely to be physiologically relevant, inherently behave as independent mechanotransducers. We propose that this property is essential for cells to transduce forces homogeneously across the entire cell membrane.</jats:p>

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10.7554/elife.70988

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Lewis, Amanda H, and Jörg Grandl (n.d.). Piezo1 ion channels inherently function as independent mechanotransducers. eLife, 10. 10.7554/elife.70988 Retrieved from https://hdl.handle.net/10161/23957.

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Grandl

Jorg Grandl

Associate Professor of Neurobiology

I am a biophysicist, Associate Professor of Neurobiology, and Director of Neurobiology Graduate Studies at Duke University. I received my PhD from the Ecole Polytéchnique Fédérale de Lausanne (EPFL), Switzerland and completed an NIH Ruth L. Kirschstein Postdoctoral Fellowship with Nobel Laureate Ardem Patapoutian at Scripps, La Jolla.

My research investigates the biophysics of force-gated ion channels and cellular mechanotransduction. This work produced over 30 publications, including in Nature, Nature Neuroscience, Neuron, and eLife. My past trainees have continued scientific training at academic institutions such as Harvard, The Broad Institute, MD Anderson, and Yale, or in the private biomedical sector. Further, I served on study sections for NIH R01, R03, R35, R00/K99, F32 and P20 awards, and for the German Research Foundation (DFG) Emmy Noether Award, and I regularly peer-review manuscripts for Nature, Science, Neuron, eLife, PNAS, and others.

As the Director of Duke Neurobiology Graduate Studies, I currently serve 47 intellectually diverse faculty from 15 Departments, who hold over $42M (or $900K per investigator) in research support, and 67 graduate trainees, who over the past 5 years have published 130 research articles and won 31 individual fellowships. In this capacity I oversee, coordinate, and direct all daily aspects of the Duke Neurobiology Graduate Training Program.


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