Cellular microenvironment is crucial in determining cell fate and function. Cells have the ability to perceive and respond to various extracellular chemical and mechanical stimuli. These stimuli trigger complex intracellular signaling pathways that have evolved to help maintain cellular homeostasis. Nucleolus, a prominent sub-nuclear organelle, has been established as a hub that coordinates cellular stress response pathways. Due to its dynamic properties, the nucleolus has been shown to rapidly respond to various extracellular stressors. A previous study within our team revealed that static mechanical compression of epithelial monolayer triggers changes in the regulation of genes encoding ribosomal proteins, suggesting a potential mechanical regulation of the ribosome biogenesis process. Here, we investigate the nucleolar state when exposed to a static compressive force. Live cell imaging was performed to observe the dynamic changes in the nucleolar composition during mechanical stress response and the possible biomechanical triggers involved. Functional consequences were investigated by performing Click-IT RNA Imaging Assay and Immunofluorescence which revealed changes in the rate of transcription of rDNA and associated histone modifications. We conclude that external biomechanical stress triggers dynamic changes in the nucleolar composition and function which may be significant in the mechanical stress response pathway.
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