Department of Anesthesiology, Weill Cornell Medicine, New York, NY, USA.
Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY, USA.
Nature. 2019 Sep;573(7773):230-234. doi: 10.1038/s41586-019-1499-2. Epub 2019 Aug 21.
PIEZO1 is a mechanosensitive channel that converts applied force into electrical signals. Partial molecular structures show that PIEZO1 is a bowl-shaped trimer with extended arms. Here we use cryo-electron microscopy to show that PIEZO1 adopts different degrees of curvature in lipid vesicles of different sizes. We also use high-speed atomic force microscopy to analyse the deformability of PIEZO1 under force in membranes on a mica surface, and show that PIEZO1 can be flattened reversibly into the membrane plane. By approximating the absolute force applied, we estimate a range of values for the mechanical spring constant of PIEZO1. Both methods of microscopy demonstrate that PIEZO1 can deform its shape towards a planar structure. This deformation could explain how lateral membrane tension can be converted into a conformation-dependent change in free energy to gate the PIEZO1 channel in response to mechanical perturbations.
PIEZO1 是一种机械敏感通道，可将施加的力转换为电信号。部分分子结构表明，PIEZO1 是一种具有延伸臂的碗状三聚体。在这里，我们使用冷冻电子显微镜来显示 PIEZO1 在不同大小的脂质小泡中采用不同程度的曲率。我们还使用高速原子力显微镜来分析 PIEZO1 在云母表面膜上受力下的变形性，并表明 PIEZO1 可以可逆地压平到膜平面。通过近似施加的绝对力，我们估计了 PIEZO1 的机械弹簧常数的一系列值。两种显微镜方法都表明，PIEZO1 可以将其形状变形为平面结构。这种变形可以解释侧向膜张力如何转化为构象依赖性自由能变化，以响应机械扰动来门控 PIEZO1 通道。
