ArticleScience advances2025
Regulation of PIEZO1 channel force sensitivity by interblade handshaking.
Article in Science advances, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed.
- State-dependent binding of the wedge domain controls inactivation of the mechanosensitive ion channel PIEZO1.Nature communications · 2026Article
- Lipid Regulation of Mechanosensitive Ion Channels.International journal of molecular sciences · 2026Review
- Structures of invertebrate PEZO-1 isoforms with a compact architecture and a dispensable pore-distal N-terminal blade.Cell reports · 2026Article
- Piezo1-mediated mechanotransduction and metabolic regulation in bone health: molecular mechanisms and implications for bone disorders.Frontiers in cell and developmental biology · 2026Review
- Platelet-Rich Plasma (PRP) bidirectionally modulates scar formation via the Piezo1-YAP/TAZ axis: a novel mechanotransduction hypothesis.Frontiers in cell and developmental biology · 2026Article
- PIPProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Endothelial Arf6 sustains capillary electrical signaling and cerebral blood flow through PIPbioRxiv : the preprint server for biology · 2025Article
- 3D-MINFLUX nanoscopy reveals distinct allosteric mechanisms for activation and modulation of PIEZO1 by Yoda1.Nature communications · 2025Article
- PIEZO Force Sensing in Vascular Biology: An Explosion of New Knowledge, Concepts and Opportunity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Cluster nanoarchitecture and structural diversity of PIEZO1 at rest and during activation in intact cells.Science advances · 2025Article
- Mechanosensitive channel Piezo1 in calcium dynamics: structure, function, and emerging therapeutic strategies.Frontiers in molecular biosciences · 2025Review
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Authors and funding
11 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
PIEZOs form trimeric calcium-permeable nonselective cationic channels that serve mechanical sensing needs across eukaryotic biology. Forces act on the channels by causing their curved blades to flatten and decompact, leading to an activated state, but it is unclear how this is regulated to enable the channels to adapt to different contexts. To identify potential mechanisms, we performed coarse-grained and all-atom molecular dynamics simulations on human PIEZO1. We observed an interblade handshake interaction mediated by basic amino acid residues in two flexible helices coordinated with regulated anionic lipid phosphatidylinositol 4,5-bisphosphate. The interaction determined the resting configuration of the channel, blade curvature, compactness, and ion pore structure. In experiments, disruption of the handshake by neutralization of helix amino acids or phosphatidylinositol 4,5-bisphosphate depletion increased the channel's sensitivity to membrane tension. Structural and amino acid sequence analysis for multiple PIEZOs predicted helix amino acid arrangements for varied handshaking intensity. We suggest a dynamic interaction in PIEZO channels that regulates force sensitivity.
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