ArticleIntegrative biology : quantitative biosciences from nano to macro2015
Extracellular matrix stiffness modulates VEGF calcium signaling in endothelial cells: individual cell and population analysis.
Article in Integrative biology : quantitative biosciences from nano to macro, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 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
18 citing papers in PubMed, 27 citations in OpenAlex.
- Fibronectin Mediates Endothelial-to-Mesenchymal Transition in Retina Angiogenesis.Investigative ophthalmology & visual science · 2025Article
- Endoplasmic reticulum stress and exosomes secretion in the pathogenesis of inflammatory bowel disease: a concise summary of research findings.Frontiers in pharmacology · 2025Review
- Clinical and biochemical characteristics for patients with polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes syndrome: a pilot observational study.Frontiers in neurology · 2025Article
- Microvascular endothelial cells display organ-specific responses to extracellular matrix stiffness.Current research in physiology · 2025Article
- Diverse calcium signaling profiles regulate migratory behavior in avascular wound healing and aberrant signal hierarchy occurs early in diabetes.American journal of physiology. Cell physiology · 2024Article
- LATS1 controls CTCF chromatin occupancy and hormonal response of 3D-grown breast cancer cells.The EMBO journal · 2024Article
- Influence of PHA Substrate Surface Characteristics on the Functional State of Endothelial Cells.Journal of functional biomaterials · 2023Article
- Matrix anisotropy promotes angiogenesis in a density-dependent manner.American journal of physiology. Heart and circulatory physiology · 2022Article
- Age Dependent Changes in Corneal Epithelial Cell Signaling.Frontiers in cell and developmental biology · 2022Article
- Attachment of cartilage wear particles to the synovium negatively impacts friction properties.Journal of biomechanics · 2021Article
- Pannexin1: Role as a Sensor to Injury Is Attenuated in Pretype 2 Corneal Diabetic Epithelium.Analytical cellular pathology (Amsterdam) · 2021Article
- Multiple Imaging Modalities for Cell-Cell Communication via Calcium Mobilizations in Corneal Epithelial Cells.Methods in molecular biology (Clifton, N.J.) · 2021Article
- Changes in Epithelial and Stromal Corneal Stiffness Occur with Age and Obesity.Bioengineering (Basel, Switzerland) · 2020Article
- Vascularization in tissue engineering: fundamentals and state-of-art.Progress in biomedical engineering (Bristol, England) · 2020Article
- Hypoxia Induced Heparan Sulfate Primes the Extracellular Matrix for Endothelial Cell Recruitment by Facilitating VEGF-Fibronectin Interactions.International journal of molecular sciences · 2019Article
- Sustained Ca2+ mobilizations: A quantitative approach to predict their importance in cell-cell communication and wound healing.PloS one · 2019Article
- Cell-cell junctional mechanotransduction in endothelial remodeling.Cellular and molecular life sciences : CMLS · 2017Review
- VEGF and VEGFR2 bind to similar pH-sensitive sites on fibronectin, exposed by heparin-mediated conformational changes.The Journal of biological chemistryArticle
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Vascular disease and its associated complications are the number one cause of death in the Western world. Both extracellular matrix stiffening and dysfunctional endothelial cells contribute to vascular disease. We examined endothelial cell calcium signaling in response to VEGF as a function of extracellular matrix stiffness. We developed a new analytical tool to analyze both population based and individual cell responses. Endothelial cells on soft substrates, 4 kPa, were the most responsive to VEGF, whereas cells on the 125 kPa substrates exhibited an attenuated response. Magnitude of activation, not the quantity of cells responding or the number of local maximums each cell experienced distinguished the responses. Individual cell analysis, across all treatments, identified two unique cell clusters. One cluster, containing most of the cells, exhibited minimal or slow calcium release. The remaining cell cluster had a rapid, high magnitude VEGF activation that ultimately defined the population based average calcium response. Interestingly, at low doses of VEGF, the high responding cell cluster contained smaller cells on average, suggesting that cell shape and size may be indicative of VEGF-sensitive endothelial cells. This study provides a new analytical tool to quantitatively analyze individual cell signaling response kinetics, that we have used to help uncover outcomes that are hidden within the average. The ability to selectively identify highly VEGF responsive cells within a population may lead to a better understanding of the specific phenotypic characteristics that define cell responsiveness, which could provide new insight for the development of targeted anti- and pro-angiogenic therapies.
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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.