ArticleScientific reports2020
Mechanobiological regulation of placental trophoblast fusion and function through extracellular matrix rigidity.
Article in Scientific reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 47 citations in OpenAlex.
- Advantages, limitations, and innovative considerations for established and emerging models of human placental syncytiotrophoblast.Human reproduction update · 2026Review
- Biophysical Considerations in Cell Fusion.Advances in experimental medicine and biology · 2026Review
- The Role of Biomechanical Regulation in Physiological and Pathological Pregnancy: From Mechanotransduction to Clinical Implications.International journal of biological sciences · 2026Review
- Unraveling the Matrix: Proteomic Profiling Reveals Stromal ECM Dysregulation in Severe Early-Onset Fetal Growth Restriction.International journal of molecular sciences · 2025Article
- Mechanosensing of Shear Stress and Uterine Spiral Artery Remodeling by Invasive Trophoblasts in Early Pregnancy.International journal of molecular sciences · 2025Review
- Matrix directs trophoblast differentiation in a bioprinted organoid model of early placental development.Nature communications · 2025Article
- PIEZO1 drives trophoblast fusion and placental development.Nature communications · 2025Article
- Article
- Histochemical Assessment of Reticulin-Collagen Patterns in the Mid-Secretory Endometrium Predicts Recurrent Pregnancy Loss.Pathophysiology : the official journal of the International Society for Pathophysiology · 2025Article
- Cell fusion dynamics: mechanisms of multinucleation in osteoclasts and macrophages.Inflammation and regeneration · 2024Review
- Review
- Directed biomechanical compressive forces enhance fusion efficiency in model placental trophoblast cultures.Scientific reports · 2024Article
- An Assessment of the Mechanophysical and Hormonal Impact on Human Endometrial Epithelium Mechanics and Receptivity.International journal of molecular sciences · 2024Article
- Controlling placental spheroid growth and phenotype using engineered synthetic hydrogel matrices.Biomaterials science · 2024Article
- Developmental transcriptomic patterns can be altered by transgenic overexpression of Uty.Scientific reports · 2023Article
- Article
- Mechanistic insights into the development of severe fetal growth restriction.Clinical science (London, England : 1979) · 2023Review
- Stiff Extracellular Matrix Promotes Invasive Behaviors of Trophoblast Cells.Bioengineering (Basel, Switzerland) · 2023Article
- Roadmap on biomaterials for women's health.JPhys materials · 2023Article
- Multinucleated Giant Cells: Current Insights in Phenotype, Biological Activities, and Mechanism of Formation.Frontiers in cell and developmental biology · 2022Review
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The syncytiotrophoblast is a multinucleated layer that plays a critical role in regulating functions of the human placenta during pregnancy. Maintaining the syncytiotrophoblast layer relies on ongoing fusion of mononuclear cytotrophoblasts throughout pregnancy, and errors in this fusion process are associated with complications such as preeclampsia. While biochemical factors are known to drive fusion, the role of disease-specific extracellular biophysical cues remains undefined. Since substrate mechanics play a crucial role in several diseases, and preeclampsia is associated with placental stiffening, we hypothesize that trophoblast fusion is mechanically regulated by substrate stiffness. We developed stiffness-tunable polyacrylamide substrate formulations that match the linear elasticity of placental tissue in normal and disease conditions, and evaluated trophoblast morphology, fusion, and function on these surfaces. Our results demonstrate that morphology, fusion, and hormone release is mechanically-regulated via myosin-II; optimal on substrates that match healthy placental tissue stiffness; and dysregulated on disease-like and supraphysiologically-stiff substrates. We further demonstrate that stiff regions in heterogeneous substrates provide dominant physical cues that inhibit fusion, suggesting that even focal tissue stiffening limits widespread trophoblast fusion and tissue function. These results confirm that mechanical microenvironmental cues influence fusion in the placenta, provide critical information needed to engineer better in vitro models for placental disease, and may ultimately be used to develop novel mechanically-mediated therapeutic strategies to resolve fusion-related disorders during pregnancy.
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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.