Lipid composition and mechanical force underlie multi-modal regulation of Piezo1 gating

Piezo1 ion channels are widely expressed cellular mechanosensors. They adopt an intrinsically curved shape when closed and are thought to open when mechanical forces applied to the membrane favor a more flattened conformation. By reconstituting Piezo1 channels into lipid vesicles, a flattened conformation has been determined, however, the ion conduction pore remained closed. In line with this observation, Piezo1 channels do not exhibit mechanical activation in the kind of lipids used in the structural studies. Here we show first that Piezo1 channels in cell-derived membranes retain functional mechanical gating, and second, that in cell-derived membranes they adopt a completely flattened disk shape associated with large conformational changes within and around the ion conduction pathway. These conformational changes occurring in cell-derived lipid membranes, suggest that mechanical force is necessary but insufficient, and that a specific membrane-derived cofactor apparently complements m..., , # Data from: Lipid composition and mechanical force underlie multi-modal regulation of Piezo1 gating Dataset DOI: [10.5061/dryad.xgxd254wg](https://doi.org/10.5061/dryad.xgxd254wg) ## Description of the data and file structure Data from electrophysiology experiments as described in the results and methods section of the manuscript. ### Files and variables #### File: Source_Data_File_SciAdv2026_.xlsx **Description:** One Excel spreadsheet, with separate tabs for each figure, listed in the order the appear in the manuscript. Details of data pertaining to each figure below:  **Fig1D: **Single channel patch-clamp recording of a patch excised from a GPMV overexpressing mPiezo1. Count = number of data points falling into given amplitude bin pA = amplitude of current recorded **Fig1F:** Comparison of peak current measured in membrane patches excised from GPMVs which are untransfected or overexpressing mPiezo1. The measurement was made holding at +60 mV and -60 mmHg. Mean..., ,Piezo1离子通道（Piezo1 ion channels）是一类广泛表达的细胞力学感受器。其在关闭状态下呈固有弯曲构象，一般认为当施加于膜的机械力倾向于使其变为更扁平的构象时，通道即开放。研究人员曾将Piezo1通道重构至脂质囊泡中，解析出了其扁平构象，但此时离子传导孔道仍处于关闭状态。与该观测结果一致的是，在结构研究所用的脂质体系中，Piezo1通道并未表现出机械激活特性。本研究首先证实，细胞来源膜中的Piezo1通道保留了功能性机械门控活性；其次发现，在细胞来源膜中，该通道会呈现完全扁平的圆盘状构象，伴随离子传导通路内部及周边发生大规模构象变化。在细胞来源脂质膜中发生的这些构象变化表明，机械力是Piezo1通道激活的必要而非充分条件，且似乎需要一种特定的膜来源辅因子来完成激活过程…… # 数据来源：《脂质组成与机械力是Piezo1门控多模态调控的基础》 数据集DOI：[10.5061/dryad.xgxd254wg](https://doi.org/10.5061/dryad.xgxd254wg) ## 数据与文件结构说明 本数据集包含论文结果与方法部分所述的电生理实验数据。 ### 文件与变量说明 #### 文件：Source_Data_File_SciAdv2026_.xlsx **描述：** 本Excel表格包含对应论文各图的独立工作表，按论文中出现的顺序排列。各图对应数据详情如下： **图1D：** 从过表达mPiezo1的GPMV上剥离的膜片单通道膜片钳记录。 Count：落入指定振幅区间的数据点数量 pA：记录的电流振幅 **图1F：** 对比未转染或过表达mPiezo1的GPMV剥离膜片中测得的峰值电流。实验于+60 mV钳制电位及-60 mmHg压力下完成。 Mean..., ,