πŸ“° "Hierarchical phase transitions as mechanical checkpoints of intracellular organization"
https://arxiv.org/abs/2408.14242
#Q-Bio.Cb #Q-Bio.Sc #Q-Bio.Mn #Actin
Hierarchical phase transitions as mechanical checkpoints of intracellular organization

Living cells inherently reorganize their intracellular structures in response to mechanical cues from their environment. Among these responses, the formation of actin-based stress fibers exhibits a series of structural transitions depending on substrate stiffness: from disordered states on soft substrates, to partial alignment, and eventually to bundled formations as stiffness increases. While these transformations have been well documented in many cell types, the physical principles underlying their emergence remain elusive. Here, we observe identical stiffness-dependent actin reorganizations in senescent fibroblasts despite their diminished biochemical and metabolic activities, suggesting that physical constraints play a dominant role in the phenomenon. We then develop a statistical-mechanical framework to demonstrate that these changes arise through a hierarchy of threshold-dependent phase transitions dictated by energy-entropy competition. This formulation provides a thermodynamic basis for understanding how distinct cytoskeletal orders become favored under different mechanical regimes. We propose that these transitions serve as mechanical checkpoints that coordinate intracellular organization during G1-phase spreading. These findings reveal how mechanical cues guide distinct intracellular orders through a physically constrained hierarchy of transitions.

arXiv.org
πŸ“° "Hierarchical phase transitions as mechanical checkpoints of intracellular organization"
https://arxiv.org/abs/2408.14242 #Mechanical #Q-Bio.Cb #Q-Bio.Sc #Q-Bio.Mn #Actin
Hierarchical phase transitions as mechanical checkpoints of intracellular organization

Living cells inherently reorganize their intracellular structures in response to mechanical cues from their environment. Among these responses, the formation of actin-based stress fibers exhibits a series of structural transitions depending on substrate stiffness: from disordered states on soft substrates, to partial alignment, and eventually to bundled formations as stiffness increases. While these transformations have been well documented in many cell types, the physical principles underlying their emergence remain elusive. Here, we observe identical stiffness-dependent actin reorganizations in senescent fibroblasts despite their diminished biochemical and metabolic activities, suggesting that physical constraints play a dominant role in the phenomenon. We then develop a statistical-mechanical framework to demonstrate that these changes arise through a hierarchy of threshold-dependent phase transitions dictated by energy-entropy competition. This formulation provides a thermodynamic basis for understanding how distinct cytoskeletal orders become favored under different mechanical regimes. We propose that these transitions serve as mechanical checkpoints that coordinate intracellular organization during G1-phase spreading. These findings reveal how mechanical cues guide distinct intracellular orders through a physically constrained hierarchy of transitions.

arXiv.org
πŸ“° "CXCL-CXCR2 signaling drives cancer-endothelium interactions in SCLC metastatic seeding"
https://www.biorxiv.org/content/10.64898/2026.04.15.716394v1?rss=1
#Actin
πŸ“° "Distinct long-term effects on lung function and airway remodeling in ovalbumin and house dust mite mouse models of experimental asthma"
https://doi.org/doi:10.1038/s41598-026-47822-x
https://pubmed.ncbi.nlm.nih.gov/42000816/
#Actin
πŸ“° "Oncogenic Ras-Src-cortactin signaling rewires actin-generated forces to drive basement membrane rupture and initiate breast cancer invasion"
https://www.biorxiv.org/content/10.64898/2026.04.15.717430v1?rss=1 #Mechanotransduction #Extracellular #Actin
πŸ“° "Oncogenic Ras-Src-cortactin signaling rewires actin-generated forces to drive basement membrane rupture and initiate breast cancer invasion"
https://www.biorxiv.org/content/10.64898/2026.04.15.717430v1?rss=1
#Myosin #Actin
πŸ“° "MTSS1-dependent ubiquitin modifications mediated by FBXO44 remodel the actin cytoskeleton to promote gastric cancer progression"
https://doi.org/doi:10.1186/s12943-026-02668-9
https://pubmed.ncbi.nlm.nih.gov/41998764/
#Actin
MTSS1-dependent ubiquitin modifications mediated by FBXO44 remodel the actin cytoskeleton to promote gastric cancer progression - Molecular Cancer

Dynamic cytoskeletal homeostasis drives malignant transformation in tumor cells and represents a therapeutic vulnerability. Therapeutic targeting of this e

SpringerLink
LIS1 is critical for axon integrity in adult mice

Mutations in human LIS1 cause lissencephaly, a severe developmental brain malformation. Although most studies focus on development, LIS1 is also expressed in adult mouse tissues. We previously induced LIS1 knockout (iKO) in adult mice using a Cre-Lox approach with an actin promoter driving CreERT2 expression. This proved to be rapidly lethal, with evidence pointing toward nervous system dysfunction. CreERT2 activity was observed in astrocytes, brainstem and spinal motor neurons, and axons and Schwann cells in the sciatic and phrenic nerves, suggesting dysfunctional cardiorespiratory and motor circuits. However, it is unclear how LIS1 knockout in these different cell types contributes to the lethal phenotype. We now report that LIS1 depletion from astrocytes is not lethal to mice (male or female), although glial fibrillary protein (GFAP) expression is increased in all LIS1-depleted astrocytes. In contrast, LIS1 depletion from projection neurons causes motor deficits and rapid lethality in both males and females. This is accompanied by progressive, widespread axonal degeneration along the entire length of both motor and sensory axons. Interestingly, sensory neurons harvested from iKO mice initially extend axons in culture but soon develop axonal swellings and fragmentation, indicating axonal degeneration. LIS1 is a prominent regulator of cytoplasmic dynein 1 (dynein, hereafter), a microtubule motor whose disruption can cause both cortical malformations and later-onset neurodegenerative diseases, such as Charcot-Marie-Tooth disease. Our results raise the possibility that LIS1 depletion, through disruption of dynein function in mature axons, may lead to Wallerian-like axon degeneration without traumatic nerve injury. Significance Statement A healthy nervous system requires that proper brain wiring is maintained throughout the life of the animal. Connectivity often involves the long axons of projection neurons. Some axons drive cognition, others contribute to sensory and motor systems, while still others subserve vitally important cardiorespiratory processes. We show that LIS1, a protein linked to congenital brain abnormalities, also plays a crucial role in fully developed projection neurons in the adult mouse. LIS1 depletion from these cells causes severe axonal degeneration resembling the Wallerian degeneration that occurs in response to nerve injury. Because LIS1 regulates dynein, and because defective dynein can cause neurodegenerative disorders in humans, our study suggests that drugs targeting Wallerian degeneration may have therapeutic potential for dynein-related diseases.

Journal of Neuroscience
πŸ“° "Pear PbrPRKs regulate pollen tube growth via modulation of apical actin and reactive oxygen species homeostasis"
https://doi.org/doi:10.1016/j.plantsci.2026.113155
https://pubmed.ncbi.nlm.nih.gov/41997500/
#Actin
πŸ“° "SMARCA2 PROTAC-dendrimer conjugates for the treatment of non-small cell lung cancer"
https://doi.org/doi:10.1016/j.xphs.2026.104286
https://pubmed.ncbi.nlm.nih.gov/41997423/
#Actin