Create accountLogin

Recent searches

No recent searches

Search options

Only available when logged in.
universeodon.com is part of the decentralized social network powered by Mastodon.
Be one with the #fediverse. Join millions of humans building, creating, and collaborating on Mastodon Social Network. Supports 1000 character posts.

Administered by:

Server stats:

3.5K
active users
Learn more

universeodon.com: AboutStatusProfiles directoryPrivacy policy

Mastodon: AboutGet the appKeyboard shortcutsView source codev4.2.17

#actin

1 post1 participant0 posts today
Rxiv mechanobio

📰 "Regulation of plasma membrane tension through hydrostatic pressure and actin protrusion forces"
biorxiv.org/content/10.1101/20 #Extracellular #Mechanical #Actin

bioRxiv · Regulation of plasma membrane tension through hydrostatic pressure and actin protrusion forcesThe plasma membrane and its associated proteins form a critical signaling hub, mediating communication between the extracellular environment and the intracellular space. Previous research suggests that both membrane trafficking and signaling activity are influenced by mechanical tension in the plasma membrane. Despite its importance, the mechanisms by which cells regulate membrane tension remain poorly understood. Using the optical tension sensor FliptR and AFM-assisted tether force measurements, we investigate plasma membrane tension regulation in mitotic cells by measuring tension changes following cytoskeletal and cell shape perturbations. Our findings show that in both assays, reported tensions are critically influenced by the cytoskeleton, however, with partially deviating trends highlighting the conceptual differences between bare and apparent membrane tension. By integrating experimental data with theoretical modeling, we demonstrate that the actin cytoskeleton regulates bare membrane tension through two distinct mechanisms: (i) modulation of intracellular hydrostatic pressure and (ii) adjustment of polymerization forces in actin-rich finger-like protrusions. ### Competing Interest Statement The authors have declared no competing interest.
Rxiv mechanobio

📰 "Time irreversibility, entropy production and effective temperature are independently regulated in the actin cortex of living cells"
arxiv.org/abs/2503.17016 #Physics.Bio-Ph #Cytoskeletal #Dynamics #Actin

arXiv logo
arXiv.orgTime irreversibility, entropy production and effective temperature are independently regulated in the actin cortex of living cellsLiving cells exhibit non-equilibrium dynamics emergent from the intricate interplay between molecular motor activity and its viscoelastic cytoskeletal matrix. The deviation from thermal equilibrium can be quantified through frequency-dependent effective temperature or time-reversal symmetry breaking quantified e.g. through the Kullback-Leibler divergence. Here, we investigate the fluctuations of an AFM tip embedded within the active cortex of mitotic human cells with and without perturbations that reduce cortex activity through inhibition of material turnover or motor proteins. While inhibition of motor activity significantly reduces both effective temperature and time irreversibility, inhibited material turnover leaves the effective temperature largely unchanged but lowers the time irreversibility and entropy production rate. Our experimental findings in combination with a minimal model highlight that time irreversibility, effective temperature and entropy production rate can follow opposite trends in active living systems, challenging in particular the validity of effective temperature as a proxy for the distance from thermal equilibrium. Furthermore, we propose that the strength of thermal noise and the occurrence of time-asymmetric deflection spikes in the dynamics of regulated observables are inherently coupled in living systems, revealing a previously unrecognized link between entropy production and time irreversibility.
Rxiv mechanobio

📰 "Actin crosslinking is required for force sensing at tricellular junctions"
biorxiv.org/content/10.1101/20 #Mechanical #Force #Actin #Cell

bioRxiv · Actin crosslinking is required for force sensing at tricellular junctionsMechanical forces are essential for tissue morphogenesis, but risk causing ruptures that could compromise tissue function. In epithelial tissues, adherens junctions withstand the forces that drive morphogenesis by recruiting proteins that stabilize cell adhesion and reinforce connections to the actin cytoskeleton under tension. However, how junctional actin networks respond to forces in vivo is not well understood. Here we show that the actin crosslinker Fimbrin is recruited to tricellular junctions under tension and plays a central role in amplifying actomyosin contractility and stabilizing cell adhesion. Loss of Fimbrin results in a failure to reorganize actin under tension and an inability to enhance myosin-II activity and recruit junction-stabilizing proteins in response to force, disrupting cell adhesion. Conversely, increasing Fimbrin activity constitutively activates force-response pathways, aberrantly stabilizing adhesion. These results demonstrate that Fimbrin-mediated actin crosslinking is an essential step in modulating actomyosin dynamics and reinforcing cell adhesion under tension during epithelial remodeling. ### Competing Interest Statement The authors have declared no competing interest.
Rxiv mechanobio

📰 "Mouse scalp development requires Rac1 and SRF for the maintenance of mechanosensing mesenchyme"
biorxiv.org/content/10.1101/20 #Mechanosensing #Mechanical #Actin

bioRxiv · Mouse scalp development requires Rac1 and SRF for the maintenance of mechanosensing mesenchymeRegulation of essential cellular responses like proliferation, migration, and differentiation is crucial for normal development. Rac1, a ubiquitously expressed small GTPase, executes these responses under the regulation of guanine nucleotide exchange factors (GEFs) and GTPase activating proteins (GTPases). Mutations in specific GEFs (DOCK6) and GTPases (AHGAP31) that regulate Rac1 are associated with Adams-Oliver syndrome (AOS), a developmental syndrome characterized by congenital scalp defects and limb truncations. Genetic ablation of Rac1 in the mouse embryonic limb ectoderm results in limb truncation. However, the etiology of Rac1-associated cranial defects is unknown. To investigate the origin and nature of cranial defects, we used a mesenchymal Cre line (Pdgfra-Cre) to delete Rac1 in cranial mesenchyme. Rac1-KO mice died perinatally and lacked the apical portion of the calvarium and overlying dermis, resembling cranial defects seen in severe cases of AOS. In control embryos, α-smooth muscle actin (αSMA) expression was spatially restricted to the apical mesenchyme, suggesting a mechanical interaction between the growing brain and the overlying mesenchyme. In Rac1-KO embryos there was reduced proliferation of apical mesenchyme, and reduced expression of αSMA and its regulator, serum response factor (SRF). Remarkably, Srf-KO mice generated with Pdgfra-Cre recapitulated the cranial phenotype observed in Rac1-KO mice. Together, these data suggest a model where Rac1 and SRF are critical to maintaining apical fibroblasts in a mechano-sensitive and proliferative state needed to complete cranial development. ### Competing Interest Statement The authors have declared no competing interest.
Rxiv cytoskeleton

📰 "Modeling the prion protein-mediated transport of extracellular vesicles on the neuron surface"
arxiv.org/abs/2502.03610
#Physics.Bio-Ph #Actin

arXiv logo
arXiv.orgModeling the prion protein-mediated transport of extracellular vesicles on the neuron surfaceNeurodegenerative diseases are among the leading causes of global mortality. They are characterized by the progressive deterioration of specific neuron populations, ultimately leading to cognitive decline and dementia. Extracellular vesicles (EVs) are crucial players in the early stages of such diseases, acting as carriers of pathogens and contributing to neuroinflammation and disease propagation. This study proposes a mathematical model to elucidate the movement of EVs bearing prion protein (PrP) on their surface along neuronal surfaces. Supported by experimental data, the model explores the role of the actin polymerization on the EVs transport dynamics. EVs isolated from non-human astrocytes were analyzed under three conditions: untreated control (Ctrl), neurons treated with Cytochalasin D (CytoD-HN), and EVs treated with Cytochalasin D (CytoD-EV). Our mathematical model effectively explained the experimental data. In the CytoD-EV dataset, EV movement was modeled using a flashing Brownian ratchet, reflecting directed movement. For active transport in the CytoD-HN set, a symmetric periodic potential models the rolling of the Evs on the neuron surface. The Ctrl scenario results in a combination of the two mechanisms. Finally, a sensitivity and comparative analysis between numerical results and experimental data showed that the model effectively replicates the Evs motion.
Rxiv mechanobio

📰 "Arp2/3-mediated bidirectional actin assembly by SPIN90 dimers in metazoans"
biorxiv.org/content/10.1101/20 #CellMigration #Actin

bioRxiv · Arp2/3-mediated bidirectional actin assembly by SPIN90 dimers in metazoansBranched actin networks nucleated by the Arp2/3 complex play critical roles in various cellular processes, from cell migration to intracellular transport. However, when activated by WISH/DIP/SPIN90 family proteins, Arp2/3 nucleates linear actin filaments. Unexpectedly, we found that human SPIN90 is a dimer that can nucleate bidirectional actin filaments. To understand the basis for this, we determined a 3 Å resolution structure of human SPIN90-Arp2/3 complex nucleating actin filaments. Our structure shows that SPIN90 dimerises via a 3-helix bundle and interacts with two Arp2/3 complexes. Each SPIN90 molecule binds both Arp2/3 complexes to promote their activation. Our analysis demonstrates that single filament nucleation by Arp2/3 is mechanistically more like branch formation than previously appreciated. The dimerisation domain in SPIN90 orthologues is conserved in metazoans, suggesting that this mode of bidirectional nucleation is a common strategy to generate anti-parallel actin filaments. ### Competing Interest Statement The authors have declared no competing interest.
Rxiv mechanobio

📰 "Intraluminal pressure triggers a rapid and persistent reinforcement of endothelial barriers"
biorxiv.org/content/10.1101/20 #Mechanical #Actin

bioRxiv · Intraluminal pressure triggers a rapid and persistent reinforcement of endothelial barriersIn response to mechanical cues, endothelial cells elicit highly sensitive cellular response pathways that contribute to the regulation of the physiology and disorders of the vascular system. However, it remains relatively unexplored how endothelial tissues process and integrate the intraluminal pressure, and in turn regulate the permeation flow across the vessel wall. Leveraging a tissue engineering approach to create microvessels (MVs), we measured real-time permeation flow induced by intraluminal pressures ranging from 0.1 to 2.0 kPa. Our findings reveal that mechanically stimulated MVs strengthen their barrier function within seconds of exposure to pressures below 1 kPa, with this enhanced barrier function persisting for 30 minutes. We demonstrate that this barrier reinforcement is linked to the closure of paracellular gaps. Additionally, we observe that it is associated with, and depends on, actin cytoskeleton reorganization, including the accumulation of stress fibers near intercellular junctions and the broadening of adherence junction protein localization. These findings provide insights into the ability of endothelial tissues to regulate interstitial fluid flow in response to sudden increases in blood pressure. ### Competing Interest Statement The authors have declared no competing interest.
Rxiv mechanobio

📰 "Druggable genome CRISPRi screen in 3D hydrogels reveals regulators of cortactin-driven actin remodeling in invading glioblastoma cells"
biorxiv.org/content/10.1101/20 #Mechanical #Actin

bioRxiv · Druggable genome CRISPRi screen in 3D hydrogels reveals regulators of cortactin-driven actin remodeling in invading glioblastoma cellsTo identify new therapeutic targets that limit glioblastoma (GBM) invasion, we applied druggable-genome CRISPR screens to patient-derived GBM cells in micro-dissectible biomimetic 3D hydrogel platforms that permit separation and independent analysis of core vs. invasive fractions. We identified 12 targets whose suppression limited invasion, of which ACP1 (LMW-PTP) and Aurora Kinase B (AURKB) were validated in neurosphere assays. Proximity labeling analysis identified cortactin as an ACP1-AURKB link, as cortactin undergoes serine phosphorylation by AURKB and tyrosine dephosphorylation by ACP1. Suppression of ACP1 or AURKB in culture and in vivo shifted the balance of cortactin phosphorylation in GBM and reduced actin polymerization and actin-cortactin co-localization. Additional biophysical analysis implicated AURKB in GBM cell adhesion and cortical stiffness, and ACP1 in resistance to mechanical stress and shape plasticity needed for 3D migration. These findings reveal a novel targetable axis that balances kinase and phosphatase activities to regulate actin polymerization during GBM invasion. ### Competing Interest Statement The authors have declared no competing interest.
ExploreLive feeds
About