📰 "Cooperative effect of local active stresses on the macroscopic contractility of elastic fiber networks"
https://arxiv.org/abs/2603.22926 #Physics.Bio-Ph #Cond-Mat.Soft #Cytoskeleton #Mechanical
Cooperative effect of local active stresses on the macroscopic contractility of elastic fiber networks

The collective action of actively contractile units embedded in elastic biopolymer networks plays a crucial role in regulating the network's macroscopic mechanical response. Here, we investigate how the macroscopic boundary stress in model elastic fiber networks depends on the number and nature of embedded contractile units, each exerting an isotropic force dipole, as well as on the bending stiffness of fibers. We find that the macroscopic stress increases nonlinearly with the number of dipoles due to mutual stiffening of initially soft, bending-dominated networks. Using effective medium theory, we relate this enhanced contractility to an increase in the effective average network coordination number due to constraints imposed by the force dipoles. By comparing three distinct force dipole models that differ in their local structures, we demonstrate that the specific manner in which an active unit constrains the network strongly influences the onset and nature of the stiffening transition. Our results highlight that not only the quantity but also the local geometry of force-generating units critically determines the macroscopic mechanical behavior. This framework provides a physical basis for understanding how biological systems-such as molecular motors in the cytoskeleton, or adherent cells in the extracellular matrix-can modulate network-scale nonlinear elastic properties through local tuning of active force-generating units.

arXiv.org
📰 "Cooperative effect of local active stresses on the macroscopic contractility of elastic fiber networks"
https://arxiv.org/abs/2603.22926
#Physics.Bio-Ph #Cond-Mat.Soft #Cytoskeleton
Cooperative effect of local active stresses on the macroscopic contractility of elastic fiber networks

The collective action of actively contractile units embedded in elastic biopolymer networks plays a crucial role in regulating the network's macroscopic mechanical response. Here, we investigate how the macroscopic boundary stress in model elastic fiber networks depends on the number and nature of embedded contractile units, each exerting an isotropic force dipole, as well as on the bending stiffness of fibers. We find that the macroscopic stress increases nonlinearly with the number of dipoles due to mutual stiffening of initially soft, bending-dominated networks. Using effective medium theory, we relate this enhanced contractility to an increase in the effective average network coordination number due to constraints imposed by the force dipoles. By comparing three distinct force dipole models that differ in their local structures, we demonstrate that the specific manner in which an active unit constrains the network strongly influences the onset and nature of the stiffening transition. Our results highlight that not only the quantity but also the local geometry of force-generating units critically determines the macroscopic mechanical behavior. This framework provides a physical basis for understanding how biological systems-such as molecular motors in the cytoskeleton, or adherent cells in the extracellular matrix-can modulate network-scale nonlinear elastic properties through local tuning of active force-generating units.

arXiv.org
📰 "The roles of the microtubule cytoskeletal network in cardiac mechanobiology"
https://doi.org/doi:10.1242/jcs.264308
https://pubmed.ncbi.nlm.nih.gov/41873788/
#Cytoskeleton #Microtubule
The roles of the microtubule cytoskeletal network in cardiac mechanobiology

Summary: Microtubules are essential cytoskeletal regulators of cardiomyocyte mechanobiology, coordinating with other cytoskeletal elements to govern both physical properties and mechanotransduction responses.

The Company of Biologists

Today's talk will be:

Isaac Wong (Dunn School, Oxford)

Mechanical Principles of Centrosome Assembly and Function

CTU 0.08/09 at 13.05

#CellBiology #cytoskeleton

📰 "Loss of Sun2 ablates nuclear mechanosensing-driven extracellular matrix production and mitigates lung fibrosis"
https://www.biorxiv.org/content/10.64898/2026.03.18.712778v1?rss=1 #Mechanosensing #Extracellular #Cytoskeleton #Mechanical
Loss of Sun2 ablates nuclear mechanosensing-driven extracellular matrix production and mitigates lung fibrosis

Fibrosis and pathological stiffening of tissue are driven by mechanical and biochemical signaling pathways. Here, we find that Sun2, an integral inner nuclear membrane component of Linker of Nucleoskeleton and Cytoskeleton (LINC) complexes, is up-regulated in the lung of patients suffering from fibrotic conditions and in fibroblasts during an injury-induced mouse model of lung fibrosis. Sun2 protein levels also increase in primary lung fibroblasts in a substrate stiffness-dependent manner. Sun2-/- primary lung fibroblasts respond to TGFβ, become contractile, and express a key marker of extracellular matrix-producing fibroblasts, Cthrc1 . Consistent with this, Sun2 is dispensable for myofibroblast formation and repairing the alveolar barrier after bleomycin injury. Remarkably, however, fibrosis does not develop in bleomycin-treated Sun2-/- mouse lungs. This is explained by the requirement for Sun2 to up-regulate genes encoding extracellular matrix proteins. We therefore suggest that Sun2-containing LINC complexes contribute to a mechanical coincidence detection mechanism that acts in concert with canonical TGFβ signaling necessary for pathologic extracellular matrix protein production, representing a nuclear mechanosensing node for intervention in fibrotic diseases of the lung. ### Competing Interest Statement The authors have declared no competing interest. National Institutes of Health, F31HL158119, F31AR085488, R35GM153474, 5R01HL163984, 1R01HL178097-01A1, R01AR076938 National Institutes of Health, https://ror.org/01cwqze88, R01AR0695505, R01AR084558

bioRxiv
📰 "SUN2 mediates epigenetic remodeling to drive mechanotransduction during skin fibrosis"
https://www.biorxiv.org/content/10.64898/2026.03.19.712957v1?rss=1
#Cytoskeleton
SUN2 mediates epigenetic remodeling to drive mechanotransduction during skin fibrosis

Fibrosis involves sustained changes in fibroblast gene expression, leading to excessive extracellular matrix (ECM) deposition and progressive tissue stiffening. Although matrix stiffness is a potent regulator of cell fate and transcription, how nuclear mechanosensing contributes to fibrosis remains unclear. Here, we define a central role for SUN2, a component of linker of nucleoskeleton and cytoskeleton (LINC) complexes, as a mediator of stiffness-dependent nuclear and chromatin responses during skin fibrosis. SUN2 transcripts are upregulated in dermal fibroblasts of patients with systemic sclerosis and Sun2 protein is elevated in fibrotic mouse skin. Nuclear size, A-type lamins and Sun2 are elevated in dermal fibroblasts plated on stiff substrates. Loss of Sun2 protects against bleomycin-induced skin fibrosis in vivo and abolishes stiffness-induced changes in nuclear size and fibrotic gene expression in vitro. Mechanistically, we identify three Sun2-dependent mechanosensitive chromatin states and show that mechanical induction of the histone methyltransferase Ezh2 requires Sun2. These findings define SUN2 as a nuclear mechanosensor that couples matrix stiffness to chromatin regulation and transcriptional programs that drive fibrosis, identifying it as a potential therapeutic target pathway in fibrotic disease. ### Competing Interest Statement The authors receive research funding from Boehringer-Ingelheim Pharmaceutical, Inc. National Institute of Arthritis and Musculoskeletal and Skin Diseases, https://ror.org/006zn3t30, AR076938, AR0695505, AR084558, AR085488 National Institute of General Medical Sciences, https://ror.org/04q48ey07, GM153474 LEO Foundation, https://ror.org/02rgsr590 Boehringer Ingelheim (Germany), https://ror.org/00q32j219

bioRxiv
📰 "Loss of Sun2 ablates nuclear mechanosensing-driven extracellular matrix production and mitigates lung fibrosis"
https://www.biorxiv.org/content/10.64898/2026.03.18.712778v1?rss=1
#Cytoskeleton
Loss of Sun2 ablates nuclear mechanosensing-driven extracellular matrix production and mitigates lung fibrosis

Fibrosis and pathological stiffening of tissue are driven by mechanical and biochemical signaling pathways. Here, we find that Sun2, an integral inner nuclear membrane component of Linker of Nucleoskeleton and Cytoskeleton (LINC) complexes, is up-regulated in the lung of patients suffering from fibrotic conditions and in fibroblasts during an injury-induced mouse model of lung fibrosis. Sun2 protein levels also increase in primary lung fibroblasts in a substrate stiffness-dependent manner. Sun2-/- primary lung fibroblasts respond to TGFβ, become contractile, and express a key marker of extracellular matrix-producing fibroblasts, Cthrc1 . Consistent with this, Sun2 is dispensable for myofibroblast formation and repairing the alveolar barrier after bleomycin injury. Remarkably, however, fibrosis does not develop in bleomycin-treated Sun2-/- mouse lungs. This is explained by the requirement for Sun2 to up-regulate genes encoding extracellular matrix proteins. We therefore suggest that Sun2-containing LINC complexes contribute to a mechanical coincidence detection mechanism that acts in concert with canonical TGFβ signaling necessary for pathologic extracellular matrix protein production, representing a nuclear mechanosensing node for intervention in fibrotic diseases of the lung. ### Competing Interest Statement The authors have declared no competing interest. National Institutes of Health, F31HL158119, F31AR085488, R35GM153474, 5R01HL163984, 1R01HL178097-01A1, R01AR076938 National Institutes of Health, https://ror.org/01cwqze88, R01AR0695505, R01AR084558

bioRxiv
📰 "Asymmetry and the cytoskeleton: Mechanisms of asymmetric neural stem cell division in Drosophila melanogaster"
https://doi.org/doi:10.1016/bs.ctdb.2025.11.002
https://pubmed.ncbi.nlm.nih.gov/41856738/
#Cytoskeleton