The role of organelles as mechanotransducers.

Abstract

Mechanobiology examines how physical forces influence cellular structure and function. Traditionally, mechanotransduction has been attributed to plasma membrane receptors, focal adhesions, and the cytoskeleton. However, emerging evidence highlights intracellular organelles as active contributors to mechanosensing and force transduction. Organelles such as the endoplasmic reticulum, nucleus, Golgi apparatus, mitochondria, and endolysosomal system possess distinct structural and biophysical properties that enable them to detect and respond to both external forces such as extracellular matrix stiffness and shear stresses and internal forces such as actomyosin contractility. This review summarizes the mechanobiological roles of major organelles, focusing on their cytoskeletal interactions, mechanosensitive channels, signaling pathways, and force-induced morphological adaptations. We also discuss inter-organelle communication under mechanical stress, including ER-mitochondria contact sites and Golgi-ER trafficking, particularly in processes such as cell migration. Additionally, we highlight recent advances in experimental and analytical approaches, including organelle-targeted Flipper-TR tension probes, optical tweezers, optogenetic force perturbation systems, and integrated single-cell omics that enable quantitative interrogation of mechanical properties and responses at subcellular resolution. Collectively, these insights position organelle mechanobiology as a critical frontier for understanding development and diseases such as cancer, fibrosis, and neurodegeneration.