THE NUCLEUS: Mechanosensing in cardiac disease

The nucleus provides a physical and selective chemical boundary to segregate the genome from the cytoplasm. The contents of the nucleus are surrounded by the nuclear envelope, which acts as a hub of mechanosensation, transducing forces from the external cytoskeleton to the nucleus, thus impacting on nuclear morphology, genome organisation, gene transcription and signalling pathways. Muscle tissues such as the heart are unique in that they actively generate large contractile forces, resulting in a distinctive mechanical environment which impacts nuclear properties, function and mechanosensing. In light of this, mutations that affect the function of the nuclear envelope (collectively known as nuclear envelopathies and laminopathies) disproportionately result in striated muscle diseases, which include dilated and arrhythmogenic cardiomyopathies. Here we review the nucleus and its role in mechanotransduction, as well as associated defects that lead to cardiac dysfunction.

Automated summary

The nucleus acts as a physical and chemical boundary to separate the genome from the cytoplasm, with the nuclear envelope playing a key role in mechanosensing and impacting nuclear morphology, gene transcription, and signaling pathways. Muscle tissues, like the heart, generate significant contractile forces that create a unique mechanical environment influencing nuclear properties and mechanosensing, with mutations affecting the nuclear envelope leading to striated muscle diseases, including cardiomyopathies. This review focuses on the role of the nucleus in mechanotransduction and associated defects that lead to cardiac dysfunction.