Search bioRxiv⌕ Search

Biology subjects

Kaluarachchi, S.

Publications and source records attributed to Kaluarachchi, S..

2 recordsLinked to original sources

Mechanical Stretch Counteracts Hypomagnetic Field-Induced Changes in YAP Nuclear Localization in C2C12 Myoblasts

The geomagnetic field (GMF) is a persistent environmental factor that influences biological processes. Reduced geomagnetic field exposure can alter cellular processes, but its effects on cellular mechanotransduction and responsiveness to mechanical stimulation remain poorly understood. Here, we developed an in vitro platform combining a programmable uniaxial stretching device with a mu-metal shielding chamber to independently manipulate mechanical stretch and magnetic field exposure. Using C2C12 myoblasts, we evaluated culture conditions and cyclic stretching parameters to identify a regimen that promoted nuclear localization of the mechanosensitive transcriptional coactivator yes-associated protein (YAP). We then compared cell and nuclear morphology and YAP nucleocytoplasmic localization under geomagnetic field (GMF) and hypomagnetic field (HMF; approximately 5 nT) conditions, with or without cyclic stretch. Under static conditions, HMF exposure increased cell and nuclear areas, promoted nuclear elongation, reduced nuclear circularity, and decreased the nuclear YAP level. Cyclic stretch induced nuclear alignment perpendicular to the stretching direction under both magnetic field conditions, without significantly altering cell or nuclear area or nuclear elongation. Importantly, cyclic stretch increased nuclear YAP localization under both GMF and HMF conditions, restoring it in HMF-exposed cells to levels comparable to those in stretched cells under GMF. These findings indicate that C2C12 myoblasts remain responsive to mechanical stimulation under HMF conditions and that cyclic stretch can counteract the HMF-associated reduction in nuclear YAP localization. Our platform provides a foundation for investigating how magnetic and mechanical cues jointly regulate myoblast behavior.

biophysics↗

Nuclear Myosin 1 links genomic architecture to adipose tissue remodeling, metabolic inflammation and obesity in mice

During adipogenesis, a metabolic shift from oxidative phosphorylation (OXPHOS) to aerobic glycolysis enables preadipocytes to meet the biosynthetic and energetic demands of differentiation. Nuclear myosin 1 (NM1), a chromatin-associated actomyosin motor that regulates transcription and chromatin accessibility, is essential for maintaining OXPHOS. Here, we identify NM1 as a key regulator of adipocyte differentiation and adipose tissue homeostasis. Integration of ATAC-seq and RNA-seq in NM1-deficient mouse embryonic fibroblasts revealed coordinated dysregulation of adipogenic genes (Insig1, Lipg, Fat1) and altered enhancer accessibility near Klf6, Foxo3, Smad5, and Gata4. NM1 knockout mesenchymal stem cells showed impaired adipogenic differentiation despite adipocyte hypertrophy. In vivo, NM1-deficient mice developed age-dependent visceral obesity with transcriptional reprogramming in white adipose tissue (WAT), including downregulation of adipogenesis and mitochondrial pathways, and activation of IFNG-, IL33-, and TNF-driven inflammation. Cross-species analysis revealed overlap with MYO1C-centered regulatory modules in human adipose tissue, implicating NM1/MYO1C in conserved chromatin-based control of adipose biology

cell biology↗