Mastodawn

📰 "Theca cell mechanosensing and regulation of follicular extracellular matrix during ovarian follicle development"
https://www.biorxiv.org/content/10.64898/2026.03.12.711479v1?rss=1 #Mechanosensing #Extracellular #Mechanical #Cell

Theca cell mechanosensing and regulation of follicular extracellular matrix during ovarian follicle development

Mammalian folliculogenesis is essential for female hormonal regulation and successful reproduction. While the steroidogenic functions of theca cells (TCs) have been implicated in ovarian diseases and infertility, the physico-structural properties of TCs and their associated extracellular matrix (ECM), or theca matrix, remain poorly understood. Using murine ovaries, we show that a stiff basement membrane (BM) and theca matrix constitute a mechanically instructive niche that modulates TC proliferation and Yes-associated protein (YAP) signalling in secondary follicles. We identify hyaluronic acid (HA) as a key matrix component that is actively secreted by contractile TCs. The HA scaffold, in turn, regulates TC proliferation, YAP signalling and motility, and is required for overall follicle growth. We showed that stiffer substrates enhance YAP nuclear transport in TCs, while mechanical stretch, cell packing, and curvature affect TC proliferation. In addition, TCs exhibit directed migration towards regions of positive curvature. Together, this study reveals a mechanochemical feedback mechanism that establishes TC mechanics and HA as key regulators of theca matrix formation that is essential for mammalian folliculogenesis. ### Competing Interest Statement The authors have declared no competing interest. National Research Foundation, NRF-MSG-2023-0001 Ministry of Eduction, Singapore, T2EP30222-0026

bioRxiv

Rxiv mechanobio 3d ago

📰 "Disruption of nuclear-cytoskeletal connection impairs epithelial cell mechanosensing and collective migration"
https://doi.org/doi:10.1016/j.bpj.2026.03.030
https://pubmed.ncbi.nlm.nih.gov/41832602/
#Mechanosensing #CellMigration #Cytoskeleton #Cytoskeletal

Rxiv mechanobio 3d ago

📰 "Marangoni-driven redistribution and activity of Piezo1 molecules in epithelial and cancer cells"
https://doi.org/doi:10.1016/j.cis.2026.103877
https://pubmed.ncbi.nlm.nih.gov/41831260/
#Mechanosensing #Cell

Rxiv mechanobio Mar 4

📰 "N-cadherin Adhesive Interactions Mechanically Modulate Phenotype of Pancreatic Stellate Cells via YAP-dependent Mechanosensing"
https://doi.org/doi:10.1002/smtd.202501659
https://pubmed.ncbi.nlm.nih.gov/41778319/
#Mechanosensing #Extracellular #Cadherin

Rxiv mechanobio Feb 20

📰 "Mechanosensing and IL-13 Signaling Synergistically Modulate Intestinal Stem Cell Differentiation via STAT6 and YAP"
https://www.biorxiv.org/content/10.64898/2026.02.19.706676v1?rss=1 #Mechanosensing #Mechanical #Cell

Mechanosensing and IL-13 Signaling Synergistically Modulate Intestinal Stem Cell Differentiation via STAT6 and YAP

A long-term complication of chronic inflammation is the mechanical stiffening of the tissue, culminating in fibrosis. Fibrosis can severely disrupt tissue function and is a major risk factor for other diseases. It is not currently well understood how fibrosis impacts the response to inflammatory signals. To address this, we investigated cross- talk between cellular mechanosensing and the response to Interleukin (IL)-13, a cytokine associated with inflammatory bowel diseases (IBDs). Using 3D intestinal organoids and organoid monolayer culture, we uncovered a synergy between mechanosensing and IL-13 signaling in regulating intestinal stem cell differentiation. Through quantitative high-resolution microscopy and functional inhibition, we found that this response requires activation of STAT6, a known mediator of IL-13. Both IL- 13 and high substrate stiffness increase cellular traction forces and focal adhesion formation, but at the expense of reduced tension at cell-cell junctions and compromised epithelial barrier function. The mechanosensing and IL-13 responses require actomyosin contractility and YAP, which is activated downstream of a positive feedback loop involving STAT6-dependent myosin-2 activation. Our results establish a novel STAT6-YAP signaling axis that integrates inflammatory and mechanical cues to regulate intestinal cell fate and barrier integrity, opening new avenues to target epithelial dysfunction in fibrosis, chronic inflammation and regenerative medicine. ### Competing Interest Statement The authors have declared no competing interest.

bioRxiv

Rxiv mechanobio Feb 11

📰 "A synNotch-based morphogen detection system reveals sFRP2 enhances Wnt3a signaling"
https://www.biorxiv.org/content/10.64898/2026.02.09.704138v1?rss=1 #Mechanosensing #Extracellular

A synNotch-based morphogen detection system reveals sFRP2 enhances Wnt3a signaling

Morphogen gradients provide essential positional information during tissue development, yet the extracellular mechanisms that regulate morphogen transport and presentation remain poorly understood. Here, we introduce a mechanosensitive detection system based on synthetic Notch (synNotch) receptors that selectively detects surface-bound, but not soluble, morphogen complexes. Applying this platform to Wnt signaling, we demonstrate that secreted Frizzled-related protein 2 (sFRP2) promotes the recruitment of Wnt3a to the cell surface via heparan sulfate proteoglycans, enabling coordinated endocytosis and robust activation of canonical Wnt/β-catenin signaling. Notably, sFRP2 extends the effective signaling range of Wnt3a and amplifies Wnt responses under ligand-limiting conditions. In intestinal organoid cultures, sFRP2 enhances Wnt3a-driven growth and induces high-Wnt morphological states with low-level Wnt concentrations. These findings identify sFRP2 as an extracellular carrier that stabilizes surface-bound Wnt3a and regulates both the strength and spatial range of Wnt signaling. More broadly, this work demonstrates the utility of synNotch mechanosensing for dissecting extracellular morphogen dynamics and highlights morphogen carrier proteins as a platform for optimizing organoid culture. ### Competing Interest Statement S.T. is an inventor on a patent for synthetic Notch receptors (Patent No.: US 10,590,182 B2) held by the Regents of the University of California, which is licensed to Gilead. K.M. declare no competing interests. Japan Science and Technology Agency, JPMJPR2147 Japan Science and Technology Agency, JPMJFR2311 Japan Society for the Promotion of Science Japan Society for the Promotion of Science, 24K02021 Exploratory Research Center on Life and Living Systems Exploratory Research Center on Life and Living Systems, 23EXC203 World Premier International Research Center Initiative (WPI), Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japan Yoshida Scholarship Foundation ANRI fellowship

bioRxiv

Rxiv mechanobio Feb 9

📰 "Integrin-Mediated Mechanosensing of Modeled Lymph Node Microenvironment Promotes T Cell Activation via Nuclear Deformation"
https://doi.org/doi:10.34133/research.1121
https://pubmed.ncbi.nlm.nih.gov/41660641/
#Mechanosensing #Mechanical #Cell

Rxiv mechanobio Feb 6

📰 "Spatial control of myosin regulatory light chain phosphorylation modulates cardiac thick filament mechanosensing"
https://doi.org/doi:10.1073/pnas.2520471123
https://pubmed.ncbi.nlm.nih.gov/41642989/
#Mechanosensing #Myosin

Rxiv mechanobio Feb 4

📰 "Cell-matrix mechanosensing and cellular metabolic demand are linked through SKT and mTORC2"
https://www.biorxiv.org/content/10.64898/2026.02.03.702586v1?rss=1 #Mechanosensing #Mechanical #Adhesion #Cell

Rxiv mechanobio Jan 16

📰 "Convergent Roles of Growth Differentiation Factor-15 (GDF-15) in Mechanotransduction, Vascular Disorganization, and Immune Suppression in Melanoma"
https://www.biorxiv.org/content/10.64898/2026.01.14.699463v1?rss=1 #Mechanotransduction #Mechanosensing #Extracellular