Mechanotransduction gone awry

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Abstract
Mechanotransduction describes the cellular processes that translate mechanical inputs into biochemical signals and can modulate cellular functions as diverse as migration, proliferation, differentiation and apoptosis. Mechanotransduction is essential in the development and maintenance of all tissues, but is particularly important in mechanically-stressed tissues such as muscle, bone, cartilage and blood vessels, as these require adaptive responses to quickly adjust to varying loading conditions. Changes in cellular or extracellular structure, the cellular mechanosensing process itself or in the relevant downstream signalling pathways can result in altered and abnormal mechanotransduction and can lead to disease. Diseases associated with disturbed mechanotransduction signalling include developmental defects, loss of hearing, muscular dystrophies, cardiac myopathies, defects in bone and cartilage, axial myopia, glaucoma, arteriosclerosis and cancer. A common denominator of many mechanobiology diseases is a disruption in the intricate force transmission between the extracellular matrix (ECM), the cytoskeleton and the nuclear interior. Sudden changes in ECM mechanics, ECM remodelling and the resultant disturbance in cytoskeletal tension and mechanotransduction signalling have emerged as important factors that can promote malignant transformation, tumorigenesis and metastasis.