Rxiv cytoskeleton45m ago
📰 "Lymphatic vessel dysfunction contributes to severe dengue pathogenesis"
https://www.biorxiv.org/content/10.64898/2026.03.27.714698v1?rss=1
#Cytoskeleton
Lymphatic vessel dysfunction contributes to severe dengue pathogenesis

Dengue virus (DENV) infection is a major global health threat, affecting more than half of the world’s population. Severe dengue is a life-threatening condition characterised by systemic bleeding, vascular leakage, and interstitial fluid accumulation that can progress to hypovolaemic shock. Circulating DENV non-structural protein 1 (NS1) has long been implicated in driving vascular hyperpermeability through its disruptive effects on endothelial cell junctions and the glycocalyx. The lymphatic system, which runs alongside the vascular network, plays a critical role in resorbing and recirculating interstitial fluid and immune cells extravasated from blood vessels. Despite its importance in maintaining tissue fluid homeostasis, the impact of dengue disease on lymphatic vessels has not previously been explored. Here, we present the first evidence that DENV-2 NS1 induces marked hyperpermeability in lymphatic endothelial cells, as measured by transendothelial electrical resistance, and impairs lymphangiogenesis in vitro. These effects were not attributable to changes in cell viability, morphology, or metabolic activity, as assessed by live/dead and metabolic assays and image analysis. Instead, we observed a defect in lymphatic endothelial cell migration, measured by scratch assay, which may underlie the reduced lymphangiogenic potential. Bulk RNA-seq, immunocytochemistry, and advanced image analysis further demonstrated pronounced reorganisation of cell–cell junctions, the cytoskeleton, and focal adhesions. Notably, junctional proteins including VE-cadherin, ZO-1, and Claudin-5 were not downregulated but instead displayed disorganised distribution along the cell junctions or aberrant cytoplasmic localisation. These structural disruptions became even more pronounced under flow conditions produced using a microfluidic system. Together, these findings demonstrate for the first time that DENV-2 NS1 directly disrupts lymphatic endothelial cell function, leading to junctional disorganisation and hyperpermeability. Such impairment of lymphatic drainage may contribute to the pathophysiology of severe dengue. ### Competing Interest Statement The authors have declared no competing interest.

bioRxiv
Rxiv mechanobio1h ago
📰 "GAPMs form a heterotrimeric complex bridging the gliding machinery and the cytoskeleton across Plasmodium species"
https://www.biorxiv.org/content/10.64898/2026.03.27.714866v1?rss=1 #Cytoskeleton #Actomyosin #Dynamics
GAPMs form a heterotrimeric complex bridging the gliding machinery and the cytoskeleton across Plasmodium species

Apicomplexan parasites, such as malaria-causing Plasmodium spp., use a specialised actomyosin motor system known as the glideosome to drive movement through host tissue and invade host cells. This system is anchored to the inner membrane complex (IMC), a series of flattened vesicles located beneath the plasma membrane, and thought to be linked to the underlying cytoskeleton by the GAPM protein family. However, it is not known how these GAPM proteins are localised across the Plasmodium life cycle, and whether different family members function alone or together. Here, we show that in two Plasmodium species GAPM2 is an IMC component whose recruitment and organisation are tightly coordinated with nuclear and cytoskeletal dynamics during parasite replication and differentiation. We find that the GAPM2 interactome remodels between asexual and sexual stages using mass spectrometry. To understand the molecular relationship between three GAPM paralogues, we solved a cryo-electron microscopy structure of the GAPM complex. This revealed an obligate heterotrimeric architecture that forms an asymmetric platform, likely to serve as a docking interface for other components of the glideosome. Finally integrating our GAPM heterotrimer structure with mass spectrometry data allowed us to propose a unified structural model of the glideosome that is conserved across apicomplexan parasites. ### Competing Interest Statement The authors have declared no competing interest. Wellcome Trust, 225292/Z/22/Z, 225844/Z/22/Z Royal Society, https://ror.org/03wnrjx87, URF\R1\211567 UK Research and Innovation, https://ror.org/001aqnf71, EP/Y036158/1 Medical Research Council, MR/K011782/1 Biotechnology and Biological Sciences Research Council, https://ror.org/00cwqg982, BB/L013827/1, BB/X014681/1 European Research Council, https://ror.org/0472cxd90, EP/X024776/1

bioRxiv
Rxiv cytoskeleton1h ago
📰 "GAPMs form a heterotrimeric complex bridging the gliding machinery and the cytoskeleton across Plasmodium species"
https://www.biorxiv.org/content/10.64898/2026.03.27.714866v1?rss=1
#Cytoskeleton #Actomyosin
GAPMs form a heterotrimeric complex bridging the gliding machinery and the cytoskeleton across Plasmodium species

Apicomplexan parasites, such as malaria-causing Plasmodium spp., use a specialised actomyosin motor system known as the glideosome to drive movement through host tissue and invade host cells. This system is anchored to the inner membrane complex (IMC), a series of flattened vesicles located beneath the plasma membrane, and thought to be linked to the underlying cytoskeleton by the GAPM protein family. However, it is not known how these GAPM proteins are localised across the Plasmodium life cycle, and whether different family members function alone or together. Here, we show that in two Plasmodium species GAPM2 is an IMC component whose recruitment and organisation are tightly coordinated with nuclear and cytoskeletal dynamics during parasite replication and differentiation. We find that the GAPM2 interactome remodels between asexual and sexual stages using mass spectrometry. To understand the molecular relationship between three GAPM paralogues, we solved a cryo-electron microscopy structure of the GAPM complex. This revealed an obligate heterotrimeric architecture that forms an asymmetric platform, likely to serve as a docking interface for other components of the glideosome. Finally integrating our GAPM heterotrimer structure with mass spectrometry data allowed us to propose a unified structural model of the glideosome that is conserved across apicomplexan parasites. ### Competing Interest Statement The authors have declared no competing interest. Wellcome Trust, 225292/Z/22/Z, 225844/Z/22/Z Royal Society, https://ror.org/03wnrjx87, URF\R1\211567 UK Research and Innovation, https://ror.org/001aqnf71, EP/Y036158/1 Medical Research Council, MR/K011782/1 Biotechnology and Biological Sciences Research Council, https://ror.org/00cwqg982, BB/L013827/1, BB/X014681/1 European Research Council, https://ror.org/0472cxd90, EP/X024776/1

bioRxiv
Rxiv mechanobio9h ago
📰 "The cytoskeleton contributes to abnormal genome-lamina interactions in LMNA-deficient cardiomyocytes"
https://doi.org/doi:10.1083/jcb.202506137
https://pubmed.ncbi.nlm.nih.gov/41891953/
#Cytoskeleton #Mechanical #Lamin
The cytoskeleton contributes to abnormal genome–lamina interactions in LMNA-deficient cardiomyocytes

Shen et al. demonstrate that LMNA reduction alters peripheral genome organization in human cardiomyocytes through cytoskeletal forces transmitted by the LI

Rockefeller University Press
Rxiv cytoskeleton9h ago
📰 "Architects of the Developing Brain: Cytoskeleton-Organizing Molecules in Neurodevelopmental Disorders"
https://doi.org/doi:10.3390/cells15060537
https://pubmed.ncbi.nlm.nih.gov/41892327/
#Cytoskeleton
Rxiv cytoskeleton9h ago
📰 "The cytoskeleton contributes to abnormal genome-lamina interactions in LMNA-deficient cardiomyocytes"
https://doi.org/doi:10.1083/jcb.202506137
https://pubmed.ncbi.nlm.nih.gov/41891953/
#Cytoskeleton #Lamin
Rxiv mechanobio19h ago
📰 "Loss of Sun2 ablates nuclear mechanosensing-driven extracellular matrix production and mitigates lung fibrosis"
https://doi.org/doi:10.64898/2026.03.18.712778
https://pubmed.ncbi.nlm.nih.gov/41889916/
#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
Rxiv cytoskeleton19h ago
📰 "SUN2 mediates epigenetic remodeling to drive mechanotransduction during skin fibrosis"
https://doi.org/doi:10.64898/2026.03.19.712957
https://pubmed.ncbi.nlm.nih.gov/41890082/
#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, it is not clear how nuclear mechanosensing contributes to fibrosis. 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
Rxiv cytoskeleton19h ago
📰 "Loss of Sun2 ablates nuclear mechanosensing-driven extracellular matrix production and mitigates lung fibrosis"
https://doi.org/doi:10.64898/2026.03.18.712778
https://pubmed.ncbi.nlm.nih.gov/41889916/
#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
Rxiv cytoskeleton1d ago
📰 "Optogenetic Tools for Spatiotemporal Interrogation of Cytoskeletal Dynamics"
https://doi.org/doi:10.1021/acs.bioconjchem.6c00071
https://pubmed.ncbi.nlm.nih.gov/41883169/
#Cytoskeleton