ArticleProceedings of the National Academy of Sciences of the United States of America2018
Platelet integrins exhibit anisotropic mechanosensing and harness piconewton forces to mediate platelet aggregation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.
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Who cites it
72 citing papers in PubMed, 175 citations in OpenAlex.
- Effects of Ligand Mobility on Ligand-Receptor Interactions Driving Integrin-Mediated Cell Adhesion.Chemical & biomedical imaging · 2026Article
- Mechanotransduction of Magnetically Applied Forces Leads to Mechanical Stiffening of Platelet-Rich Plugs.Advanced healthcare materials · 2026Article
- Biomechanical anticoagulation by spherical platelets in extracorporeal systems.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Mechanical Signaling: Molecular Mechanisms, Biological Functions, Diseases, and Therapeutic Targets.MedComm · 2025Review
- Article
- Biomechanical platelet activation: diseases that require a new class of antiplatelet therapeutics.American journal of physiology. Cell physiology · 2025Review
- Live-cell imaging of single integrin tensions with minimal background fluorescence noise.Biophysical journal · 2025Article
- Advancing Platelet Research Through Live-Cell Imaging: Challenges, Techniques, and Insights.Sensors (Basel, Switzerland) · 2025Review
- Analytical methods in studying cell force sensing: principles, current technologies and perspectives.Regenerative biomaterials · 2025Review
- Measuring Integrin Force Loading Rates Using a Two-Step DNA Tension Sensor.Journal of the American Chemical Society · 2024Article
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- Article
- Molecular Force Sensors for Biological Application.International journal of molecular sciences · 2024Review
- Unraveling the Dual-Stretch-Mode Impact on Tension Gauge Tethers' Mechanical Stability.Journal of the American Chemical Society · 2024Article
- Measuring integrin force loading rates using a two-step DNA tension sensor.bioRxiv : the preprint server for biology · 2024Article
- Can a bulky glycocalyx promote catch bonding in early integrin adhesion? Perhaps a bit.Biomechanics and modeling in mechanobiology · 2024Article
- DNA mechanocapsules for programmable piconewton responsive drug delivery.Nature communications · 2024Article
- Clots reveal anomalous elastic behavior of fiber networks.Science advances · 2024Article
- Contractility defects hinder glycoprotein VI-mediated platelet activation and affect platelet functions beyond clot contraction.Research and practice in thrombosis and haemostasis · 2024Article
- Force-Triggered Self-Destructive Hydrogels.Advanced materials (Deerfield Beach, Fla.) · 2023Article
12 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Platelet aggregation at the site of vascular injury is essential in clotting. During this process, platelets are bridged by soluble fibrinogen that binds surface integrin receptors. One mystery in the mechanism of platelet aggregation pertains to how resting platelets ignore soluble fibrinogen, the third most abundant protein in the bloodstream, and yet avidly bind immobile fibrinogen on the surface of other platelets at the primary injury site. We speculate that platelet integrins are mechanosensors that test their ligands across the platelet-platelet synapse. To investigate this model, we interrogate human platelets using approaches that include the supported lipid bilayer platform as well as DNA tension sensor technologies. Experiments suggest that platelet integrins require lateral forces to mediate platelet-platelet interactions. Mechanically labile ligands dampen platelet activation, and the onset of piconewton integrin tension coincides with calcium flux. Activated platelets display immobilized fibrinogen on their surface, thus mediating further recruitment of resting platelets. The distribution of integrin tension was shown to be spatially regulated through two myosin-signaling pathways, myosin light chain kinase and Rho-associated kinase. Finally, we discovered that the termination of integrin tension is coupled with the exposure of phosphatidylserine. Our work reveals the highest spatial and temporal resolution maps of platelet integrin mechanics and its role in platelet aggregation, suggesting that platelets are physical substrates for one another that establish mechanical feedback loops of activation. The results are reminiscent of mechanical regulation of the T-cell receptor, E-cadherin, and Notch pathways, suggesting a common feature for signaling at cell junctions.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.