ArticleJournal of cellular physiology2009
Substrate rigidity regulates Ca2+ oscillation via RhoA pathway in stem cells.
Article in Journal of cellular physiology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers.
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Who cites it
73 citing papers in PubMed, 139 citations in OpenAlex.
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- A mechanical modeling framework to study endothelial permeability.Biophysical journal · 2024Article
- ECM stiffness regulates calcium influx into mitochondria via tubulin and VDAC1 activity.Animal cells and systems · 2024Article
- From stress fiber to focal adhesion: a role of actin crosslinkers in force transmission.Frontiers in cell and developmental biology · 2024Review
- Store-Operated CaJournal of clinical medicine · 2023Review
- Balancing activation and co-stimulation of CAR tunes signaling dynamics and enhances therapeutic potency.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Article
- Cell Mechanics Regulates the Dynamic Anisotropic Remodeling of Fibril Matrix at Large Scale.Research (Washington, D.C.) · 2023Article
- Targeted Activation of G-Protein Coupled Receptor-Mediated CaTissue engineering. Part A · 2022Article
- Control of stem cell differentiation by using extrinsic photobiomodulation in conjunction with cell adhesion pattern.Scientific reports · 2022Article
- Bioelectric Dysregulation in Cancer Initiation, Promotion, and Progression.Frontiers in oncology · 2022Review
- Attachment of cartilage wear particles to the synovium negatively impacts friction properties.Journal of biomechanics · 2021Article
- Distinct calcium regulation of TRPM7 mechanosensitive channels at plasma membrane microdomains visualized by FRET-based single cell imaging.Scientific reports · 2021Article
- Substratum stiffness tunes membrane voltage in mammary epithelial cells.Journal of cell science · 2021Article
- The cellular mechanobiology of aging: from biology to mechanics.Annals of the New York Academy of Sciences · 2021Review
- Article
- Matrix stiffness regulates myocardial differentiation of human umbilical cord mesenchymal stem cells.Aging · 2020Article
13 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Substrate rigidity plays crucial roles in regulating cellular functions, such as cell spreading, traction forces, and stem cell differentiation. However, it is not clear how substrate rigidity influences early cell signaling events such as calcium in living cells. Using highly sensitive Ca(2+) biosensors based on fluorescence resonance energy transfer (FRET), we investigated the molecular mechanism by which substrate rigidity affects calcium signaling in human mesenchymal stem cells (HMSCs). Spontaneous Ca(2+) oscillations were observed inside the cytoplasm and the endoplasmic reticulum (ER) using the FRET biosensors targeted at subcellular locations in cells plated on rigid dishes. Lowering the substrate stiffness to 1 kPa significantly inhibited both the magnitudes and frequencies of the cytoplasmic Ca(2+) oscillation in comparison to stiffer or rigid substrate. This Ca(2+) oscillation was shown to be dependent on ROCK, a downstream effector molecule of RhoA, but independent of actin filaments, microtubules, myosin light chain kinase, or myosin activity. Lysophosphatidic acid, which activates RhoA, also inhibited the frequency of the Ca(2+) oscillation. Consistently, either a constitutive active mutant of RhoA (RhoA-V14) or a dominant negative mutant of RhoA (RhoA-N19) inhibited the Ca(2+) oscillation. Further experiments revealed that HMSCs cultured on gels with low elastic moduli displayed low RhoA activities. Therefore, our results demonstrate that RhoA and its downstream molecule ROCK may mediate the substrate rigidity-regulated Ca(2+) oscillation, which determines the physiological functions of HMSCs.
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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.