ArticleScience advances2018
Tensile forces drive a reversible fibroblast-to-myofibroblast transition during tissue growth in engineered clefts.
Article in Science advances, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 91 papers.
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Who cites it
91 citing papers in PubMed, 142 citations in OpenAlex.
- Physical continuity at biomaterial-ECM interfaces is associated with reduced fibroblast activation and NF-κB signaling.Biomaterials · 2026Article
- Mechanosensitive phosphorylation of NFATC4 at S213/S217 drives fibroblast-to-myofibroblast transition and fibrosis.The Journal of clinical investigation · 2026Article
- An NFATC4 phospho-switch links matrix stiffness to fibroblast fate.The Journal of clinical investigation · 2026Article
- Loss of CD44 re-educates pancreatic cancer-associated fibroblasts modulating their fibrotic and immunosuppressive functions.Cell death & disease · 2026Article
- In vitro effects of tensile strain on cancer-associated and matched normal fibroblasts derived from oral squamous cell carcinoma: an exploratory study.BMC cancer · 2026Article
- Matrix stiffness induced CREB3L1 activation contributed to skin fibrosis through calcium influx triggered endoplasmic reticulum stress.Cellular and molecular life sciences : CMLS · 2026Article
- Cell type-specific response to curvature controls tissue growth dynamics in biomaterial pores.Bioactive materials · 2026Article
- 3D-Printing-Assisted, Microfabricated Devices Reveal Hierarchical and Temporal Mechanosensing in High-Density Fibroblast Culture.ACS nano · 2026Article
- Timed Epithelial Overlay Preserves Defect Closure While Suppressing Fibrotic Remodeling in Wound Microtissues.ACS omega · 2026Article
- Human cell-derived dermal-specific interwoven extracellular matrix for diabetic wound healing.Acta biomaterialia · 2026Article
- Research progress on tumor extracellular matrix stiffness and immunosuppression.Frontiers in immunology · 2026Review
- Beyond Structure: The Dynamic Role of the Extracellular Matrix Components in Immune Evasion.Cancer communications (London, England) · 2026Review
- Unlocking the therapeutic potential of cellular mechanobiology.Science advances · 2025Review
- Fiber recruitment drives a phase transition of cell polarization at a critical cell spacing in matrix-mediated tissue remodeling.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Biophysical, cellular, and mouse model approaches to investigate the mechanical regulation of folliculogenesis.Seminars in cell & developmental biology · 2025Review
- Dynamically urethra-adapted and obligations-oriented trilayer hydrogels integrate scarless urethral repair.Nature communications · 2025Article
- Article
- The mechanobiology of fibroblast activation in disease.APL bioengineering · 2025Review
- EDA Fibronectin Microarchitecture and YAP Translocation during Wound Closure.ACS biomaterials science & engineering · 2025Article
- Micro Immune Response On-chip (MIRO) models the tumour-stroma interface for immunotherapy testing.Nature communications · 2025Article
31 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 3 institutions in 3 countries.
Funding
Abstract
Myofibroblasts orchestrate wound healing processes, and if they remain activated, they drive disease progression such as fibrosis and cancer. Besides growth factor signaling, the local extracellular matrix (ECM) and its mechanical properties are central regulators of these processes. It remains unknown whether transforming growth factor-β (TGF-β) and tensile forces work synergistically in up-regulating the transition of fibroblasts into myofibroblasts and whether myofibroblasts undergo apoptosis or become deactivated by other means once tissue homeostasis is reached. We used three-dimensional microtissues grown in vitro from fibroblasts in macroscopically engineered clefts for several weeks and found that fibroblasts transitioned into myofibroblasts at the highly tensed growth front as the microtissue progressively closed the cleft, in analogy to closing a wound site. Proliferation was up-regulated at the growth front, and new highly stretched fibronectin fibers were deposited, as revealed by fibronectin fluorescence resonance energy transfer probes. As the tissue was growing, the ECM underneath matured into a collagen-rich tissue containing mostly fibroblasts instead of myofibroblasts, and the fibronectin fibers were under reduced tension. This correlated with a progressive rounding of cells from the growth front inward, with decreased α-smooth muscle actin expression, YAP nuclear translocation, and cell proliferation. Together, this suggests that the myofibroblast phenotype is stabilized at the growth front by tensile forces, even in the absence of endogenously supplemented TGF-β, and reverts into a quiescent fibroblast phenotype already 10 μm behind the growth front, thus giving rise to a myofibroblast-to-fibroblast transition. This is the hallmark of reaching prohealing homeostasis.
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