Piezo1 as a force-through-membrane sensor in red blood cells

Piezo1 is the stretch activated Ca2+ channel in red blood cells that mediates homeostatic volume control. Here, we study the organization of Piezo1 in red blood cells using a combination of super-resolution microscopy techniques and electron microscopy. Piezo1 adopts a non-uniform distribution on the red blood cell surface, with a bias toward the biconcave 'dimple'. Trajectories of diffusing Piezo1 molecules, which exhibit confined Brownian diffusion on short timescales and hopping on long timescales, also reflect a bias toward the dimple. This bias can be explained by 'curvature coupling' between the intrinsic curvature of the Piezo dome and the curvature of the red blood cell membrane. Piezo1 does not form clusters with itself, nor does it colocalize with F-actin, Spectrin, or the Gardos channel. Thus, Piezo1 exhibits the properties of a force-through-membrane sensor of curvature and lateral tension in the red blood cell.

Automated summary

Piezo1 is a stretch-activated Ca2+ channel in red blood cells that regulates cellular volume. Using super-resolution and electron microscopy, we investigated the organization of Piezo1 in red blood cells. We found that Piezo1 exhibits a non-uniform distribution on the cell surface, with a bias towards the biconcave "dimple". The diffusion trajectories of Piezo1 molecules also indicate a preference for the dimple, which can be explained by curvature coupling between the Piezo dome and the cell membrane. Furthermore, Piezo1 does not form clusters with itself or colocalize with other cellular components. These findings suggest that Piezo1 acts as a force-through-membrane sensor for curvature and lateral tension in red blood cells.