Membrane curvature governs the distribution of Piezo1 in live cells

This study demonstrates that the curvature of the cell membrane directly regulates the spatial distribution of Piezo1, a widely expressed mechanosensitive ion channel. Piezo1 may flatten upon activation and can mechanically inhibit membrane dynamics Piezo1 is a bona fide mechanosensitive ion channel ubiquitously expressed in mammalian cells. The distribution of Piezo1 within a cell is essential for various biological processes including cytokinesis, cell migration, and wound healing. However, the underlying principles that guide the subcellular distribution of Piezo1 remain largely unexplored. Here, we demonstrate that membrane curvature serves as a key regulator of the spatial distribution of Piezo1 in the plasma membrane of living cells. Piezo1 depletes from highly curved membrane protrusions such as filopodia and enriches to nanoscale membrane invaginations. Quantification of the curvature-dependent sorting of Piezo1 directly reveals the in situ nano-geometry of the Piezo1-membrane complex. Piezo1 density on filopodia increases upon activation, independent of calcium, suggesting flattening of the channel upon opening. Consequently, the expression of Piezo1 inhibits filopodia formation, an effect that diminishes with channel activation.

Automated summary

This study shows that the curvature of the cell membrane directly affects the distribution of Piezo1, a widely expressed mechanosensitive ion channel. The density of Piezo1 increases on highly curved membrane protrusions upon activation, suggesting that the channel flattens when opened. Understanding the spatial distribution of Piezo1 can provide insights into its role in biological processes.