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Cell signalling

What physical force actually opens Piezo1?

Lewis AH, Grandl J · eLife · 2015

Open access · cc by · source: Europe PMC

In HEK293t patches, Piezo1 opened to both convex and concave stretch but tracked lateral tension with T50 ≈ 1.4 mN/m; resting tension drove inactivation and thereby tuned apparent mechanical sensitivity.

Study at a glance

Design
Animal / in-vitro — Patch-clamp plus simultaneous imaging of membrane geometry in HEK293t cells expressing mouse Piezo1, across cell-attached, inside-out, and outside-out patches
N
N=15 · Primary P50: N=15 cell-attached negative-pressure Piezo1 patches (N=12 positive); additional inside-out/outside-out and pcDNA controls
Population
HEK293t cells transiently expressing mouse Piezo1-IRES-GFP (empty-vector controls)
Outcome
Whether curvature or lateral tension opens Piezo1; T50; effect of resting tension on inactivation/availability

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Key findings

Currents appeared from −5 mmHg in cell-attached patches (P50 −16.7 ± 2.8 mmHg, N=15) and also with positive pressure. Inside-out negative P50 was −35.8 ± 4.0 mmHg (N=10). Tension for half-activation was T50 = 1.4 ± 0.1 mN/m. Resting tension inactivated channels, so flattening prepulses increased available current.

Methodology

Recorded Piezo1 stretch currents at −80 mV in three patch configurations while imaging pipette membrane geometry, converted pressure to tension via Laplace’s law, and used flattening prepulses to remove resting curvature/tension before test steps.

Limitations

Heterologous HEK patches cannot prove cytoskeleton is irrelevant in tissues, nor how Piezo1 senses tension at atomic scale; local curvature could still matter.

How this study connects

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