Calcium ions (Ca) play pivotal roles in regulating numerous cellular functions, including metabolism and growth, in normal and cancerous cells. Consequently, Ca signaling is a vital determinant of cell fate and influences both cell survival and death. These intracellular signals are susceptible to modulation by various factors, including changes in the extracellular environment, which leads to mechanical alterations. However, the effect of extracellular matrix (ECM) stiffness variations on intracellular Ca signaling remains underexplored. In this study, we aimed to elucidate the mechanisms of Ca regulation through the mitochondria, which are crucial to Ca homeostasis. We investigated how Ca regulatory mechanisms adapt to different levels of ECM stiffness by simultaneously imaging the mitochondria and endoplasmic reticulum (ER) in live cells using genetically encoded biosensors. Our findings revealed that the uptake of mitochondrial Ca through Voltage-Dependent Anion Channel 1 (VDAC1), facilitated by intracellular tubulin, is influenced by ECM stiffness. Unraveling these Ca regulatory mechanisms under various conditions offers a novel perspective for advancing biomedical studies involving Ca signaling.
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http://dx.doi.org/10.1080/19768354.2024.2393811 | DOI Listing |
Biomimetics (Basel)
January 2025
Department of Biology, Texas A&M University, 3258 TAMU, College Station, TX 77843, USA.
In this preliminary study, the long-term effects of calcium chloride crosslinking concentration on viability of 16HBE14o- human bronchial epithelial cells embedded in alginate-extracellular matrix (ECM) or alginate-methylcellulose-ECM hydrogels have been investigated. There is currently a limited understanding regarding the effects of crosslinking solution concentration on lung epithelial cells embedded in hydrogel. Furthermore, the effects of calcium chloride concentration in crosslinking solutions on other cell types have not been reported regarding whether the addition of viscosity and stiffness tuning agents such as methylcellulose will alter the responses of cells to changes in calcium chloride concentration in crosslinking solutions.
View Article and Find Full Text PDFBiomacromolecules
January 2025
Weldon School of Biomedical Engineering, Purdue University, West Lafayette, Indiana 47907, United States.
Pancreatic ductal adenocarcinoma (PDAC) is characterized by a dense extracellular matrix (ECM) exhibiting high stiffness and fast stress relaxation. In this work, gelatin-based viscoelastic hydrogels were developed to mimic the compositions, stiffness, and fast stress relaxation of PDAC tissues. The hydrogels were cross-linked by gelatin-norbornene-boronic acid (GelNB-BA), thiolated macromers, and a 1,2-diol-containing linear synthetic polymer PHD.
View Article and Find Full Text PDFFront Cell Dev Biol
January 2025
Mathematical Institute, Faculty of Science, Leiden University, Leiden, Netherlands.
Many mammalian cells, including endothelial cells and fibroblasts, align and elongate along the orientation of extracellular matrix (ECM) fibers in a gel when cultured . During cell elongation, clusters of focal adhesions (FAs) form near the poles of the elongating cells. FAs are mechanosensitive clusters of adhesions that grow under mechanical tension exerted by the cells' pulling on the ECM and shrink when the tension is released.
View Article and Find Full Text PDFArterioscler Thromb Vasc Biol
January 2025
British Heart Foundation Centre of Research Excellence, School of Cardiovascular and Metabolic Medicine & Sciences, King's College London, United Kingdom. (M.W., M.F., R.O., L.S., M.M., C.M.S.).
Background: The ECM (extracellular matrix) provides the microenvironmental niche sensed by resident vascular smooth muscle cells (VSMCs). Aging and disease are associated with dramatic changes in ECM composition and properties; however, their impact on the VSMC phenotype remains poorly studied.
Methods: Here, we describe a novel in vitro model system that utilizes endogenous ECM to study how modifications associated with age and metabolic disease impact the VSMC phenotype.
J Drug Target
January 2025
Science and Technology Department, Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning, China.
The lung tumour microenvironment (TME) is composed of various cell types, including cancer cells, stromal and immune cells, as well as extracellular matrix (ECM). These cells and surrounding ECM create a stiff, hypoxic, acidic and immunosuppressive microenvironment that can augment the resistance of lung tumours to different forms of cell death and facilitate invasion and metastasis. This environment can induce chemo/radiotherapy resistance by inducing anti-apoptosis mediators such as phosphoinositide 3-kinase (PI3K)/Akt, signal transducer and activator of transcription 3 (STAT3) and nuclear factor kappa B (NF-κB), leading to the exhaustion of antitumor immunity and further resistance to chemo/radiotherapy.
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