ArticleIntegrative biology : quantitative biosciences from nano to macro2010
Ultra-rapid activation of TRPV4 ion channels by mechanical forces applied to cell surface beta1 integrins.
Article in Integrative biology : quantitative biosciences from nano to macro, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 167 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
167 citing papers in PubMed, 281 citations in OpenAlex.
- Transforming destructive mechanical cues into therapeutic power: Activation of PIEZO1 and TRPV4 counteracts mechano-induced damage of cellular junctions in Hailey-Hailey disease.Journal of advanced research · 2026Article
- Cutaneous TRPV4 Potentiates the Afferent Transmission of Electroacupuncture Stimulation.ACS omega · 2026Article
- 25+ Years of TRPV4: From Discovery to Translational Horizons.Research square · 2026Article
- Endoplasmic reticulum stress in brain metastatic cascade.NPJ precision oncology · 2026Review
- A novel role for TRPV1 in macrophage giant cell formation.bioRxiv : the preprint server for biology · 2026Article
- Mechanoepigenetics in musculoskeletal disease.Osteoarthritis and cartilage · 2026Review
- Magnetic-topological multistage synergy: Anisotropic ovalbumin scaffolds loaded with magnetically-responsive neural cells for long-distance peripheral nerve regeneration.Bioactive materials · 2026Article
- Cell shape and maturation impacts α-actinin-2 tension in iPSC-derived cardiomyocytes.APL bioengineering · 2026Article
- Lipid Regulation of Mechanosensitive Ion Channels.International journal of molecular sciences · 2026Review
- Cellular and Molecular Mechanisms of SARS-CoV-2 Spike Protein-Induced Endothelial Dysfunction.Cells · 2026Review
- Soft tissue mechanosensing and remodeling: the core regulatory role of Piezo/TRPV4 ion channels.Frontiers in cell and developmental biology · 2026Review
- A Novel Core-Shell Hydrogel 3D Model for Studying Macrophage Mechanosensing and Foreign Body Giant Cell Formation.Advanced healthcare materials · 2026Article
- TRPV4-Mediated Mechanosensing Regulates the Endothelial-to-Mesenchymal Transition: Implications for Atherosclerosis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Integration of cAMP and TRPV4 Signaling to Optimize Collagen Remodeling for Management of Fibrosis.Cells · 2025Review
- Digital light processing of hydrogel molds to guide cell mechanosensing and the fabrication of meniscal tissue constructs.APL bioengineering · 2025Article
- Transient Receptor Potential Vanilloid 4 (TRPV4) in the Human Carotid Body.International journal of molecular sciences · 2025Article
- Transient receptor potential vanilloid 4 modulates substrate stiffness mechanosensing and transcellular pore formation in human Schlemm's canal cells.Acta biomaterialia · 2025Article
- TRPV4 activation by TGFβ2 enhances cellular contractility and drives ocular hypertension.eLife · 2025Article
- TRPV4 modulates substrate stiffness mechanosensing and transcellular pore formation in human Schlemm's canal cells.bioRxiv : the preprint server for biology · 2025Article
- Trpv4-mediated mechanotransduction regulates the differentiation of valvular interstitial cells to myofibroblasts: implications for aortic valve stenosis.American journal of physiology. Cell physiology · 2025Article
107 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 4 institutions in 2 countries.
Funding
Abstract
Integrins are ubiquitous transmembrane mechanoreceptors that elicit changes in intracellular biochemistry in response to mechanical force application, but these alterations generally proceed over seconds to minutes. Stress-sensitive ion channels represent another class of mechanoreceptors that are activated much more rapidly (within msec), and recent findings suggest that calcium influx through Transient Receptor Potential Vanilloid-4 (TRPV4) channels expressed in the plasma membrane of bovine capillary endothelial cells is required for mechanical strain-induced changes in focal adhesion assembly, cell orientation and directional migration. However, whether mechanically stretching a cell's extracellular matrix (ECM) adhesions might directly activate cell surface ion channels remains unknown. Here we show that forces applied to beta1 integrins result in ultra-rapid (within 4 msec) activation of calcium influx through TRPV4 channels. The TRPV4 channels were specifically activated by mechanical strain in the cytoskeletal backbone of the focal adhesion, and not by deformation of the lipid bilayer or submembranous cortical cytoskeleton alone. This early-immediate calcium signaling response required the distal region of the beta1 integrin cytoplasmic tail that contains a binding site for the integrin-associated transmembrane CD98 protein, and external force application to CD98 within focal adhesions activated the same ultra-rapid calcium signaling response. Local direct strain-dependent activation of TRPV4 channels mediated by force transfer from integrins and CD98 may therefore enable compartmentalization of calcium signaling within focal adhesions that is critical for mechanical control of many cell behaviors that underlie cell and tissue development.
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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.