ArticleProceedings of the National Academy of Sciences of the United States of America2006
G protein-coupled receptors sense fluid shear stress in endothelial cells.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 229 papers.
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Who cites it
229 citing papers in PubMed, 487 citations in OpenAlex.
- Vascular mechanical forces and vascular diseases.Journal of advanced research · 2026Review
- Oscillatory shear stress-driven endothelial-to-mesenchymal transition: a critical mechanical signal transduction mechanism in atherosclerosis progression.Cell death discovery · 2026Review
- Exercise-altered fluid shear stress regulates vascular endothelial inflammation via Piezo1.Frontiers in physiology · 2026Review
- The GPR68-NINJ1 axis: an emerging mechano-chemical checkpoint in blood-brain barrier disruption-a hypothetical framework and therapeutic promise.Frontiers in cellular neuroscience · 2026Article
- GABA-independent activation of GABANature communications · 2025Article
- Mechanosensing of Shear Stress and Uterine Spiral Artery Remodeling by Invasive Trophoblasts in Early Pregnancy.International journal of molecular sciences · 2025Review
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- Unraveling a Receptor-Mediated Bioluminescence Signaling Pathway in Red Tide Algae.Journal of molecular biology · 2025Article
- Diversity of Effects of Mechanical Influences on Living Systems and Aqueous Solutions.International journal of molecular sciences · 2025Review
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- A force-sensitive adhesion GPCR is required for equilibrioception.Cell research · 2025Article
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- Mechanobiology in the eye.npj biological physics and mechanics · 2025Review
- Unveiling the potential of biomechanics in pioneering innovative strategies for cancer therapy.Theranostics · 2025Review
- Tie-2 regulates endothelial morphological responses to shear stress by FOXO1-triggered autophagy.PloS one · 2025Article
- Tension at the gate: sensing mechanical forces at the blood-brain barrier in health and disease.Journal of neuroinflammation · 2024Review
- Force versus Response: Methods for Activating and Characterizing Mechanosensitive Ion Channels and GPCRs.Advanced healthcare materials · 2024Review
- Nitric oxide modelling and its bioavailability influenced by red blood cells.Journal of the Royal Society, Interface · 2024Article
- Illuminating cellular architecture and dynamics with fluorescence polarization microscopy.Journal of cell science · 2024Review
- Integrating molecular and cellular components of endothelial shear stress mechanotransduction.American journal of physiology. Heart and circulatory physiology · 2024Review
169 more citing papers are in PubMed but not listed here.
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Hemodynamic shear stress stimulates a number of intracellular events that both regulate vessel structure and influence development of vascular pathologies. The precise molecular mechanisms by which endothelial cells transduce this mechanical stimulus into intracellular biochemical response have not been established. Here, we show that mechanical perturbation of the plasma membrane leads to ligand-independent conformational transitions in a G protein-coupled receptor (GPCR). By using time-resolved fluorescence microscopy and GPCR conformation-sensitive FRET we found that stimulation of endothelial cells with fluid shear stress, hypotonic stress, or membrane fluidizing agent leads to a significant increase in activity of bradykinin B2 GPCR in endothelial cells. The GPCR conformational dynamics was detected by monitoring redistribution of GPCRs between inactive and active conformations in a single endothelial cell under fluid shear stress in real time. We show that this response can be blocked by a B(2)-selective antagonist. Our data demonstrate that changes in cell membrane tension and membrane fluidity affect conformational dynamics of GPCRs. Therefore, we suggest that GPCRs are involved in mediating primary mechanochemical signal transduction in endothelial cells. We anticipate our experiments to be a starting point for more sophisticated studies of the effects of changes in lipid bilayer environment on GPCR conformational dynamics. Furthermore, because GPCRs are a major target of drug development, a detailed characterization of mechanochemical signaling via the GPCR pathway will be relevant for the development of new antiatherosclerosis drugs.
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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.