Matrix maturation and cytoskeletal tension define strain thresholds for stretch-induced calcium signaling in human tendon cells
Jaeger, P. K.; Passini, F. S.; Niederoest, B.; Bollhalder, M.; Fucentese, S.; Snedeker, J. G.
Show abstract
The extracellular matrix (ECM) and mechanical loading shape cellular behavior, yet their interaction remains obscure. We developed a dynamic proto-tissue model using human tendon cells and live-cell calcium imaging to study how ECM and cell mechanics regulate mechanotransduction. Stretch-induced calcium signaling served as a functional readout. We discovered that ascorbic acid-dependent ECM deposition is essential for proto-tissue maturation and stretch-induced calcium signaling at physiological strains. Proto-tissue maturation enhanced stretch sensitivity, reducing the strain needed to trigger a calcium response from [~]40% in isolated cells to [~]5% in matured proto-tissues. A strong correlation between tissue rupture and calcium signaling suggests a mechanistic link to ECM damage. Disrupting ECM integrity, cell alignment, or cytoskeletal tension reduced mechanosensitivity, showcasing the influence of ECM and cytoskeletal mechanics on stretch-induced calcium signaling. Fundamentally, our work replicates calcium signaling observed in rodent tendon explants in vitro and bridges the gap between cell-scale and tissue-scale mechanotransduction. TeaserMatrix matters: tendon cells tune their response to stretch as their mechanical environment develops.
Matching journals
The top 10 journals account for 50% of the predicted probability mass.
Similar papers in this journal
Similar papers in this journal
- Toughening mechanisms for the attachment of architectured materials: The mechanics of the tendon enthesis 96%
- Oncogenic RAS instructs morphological transformation of human epithelia via differential tissue mechanics. 94%
- Biomaterials direct functional B cell response in a material specific manner 93%
Similar papers in this journal
- HIF1α gates tendon response to overload and drives tendinopathy independently of vascular recruitment 94%
- Dynamic Loading of Human Engineered Heart Tissue Enhances Contractile Function and Drives Desmosome-linked Disease Phenotype 94%
- Variants in ALDH1A2 reveal an anti-inflammatory role for retinoic acid and a new class of disease-modifying drugs in osteoarthritis 90%
Similar papers in this journal
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.