Cytoskeletal safeguards: Protecting the nucleus from mechanical perturbations

The cell nucleus plays a key role in cellular mechanoresponses. 3D genome organisation, gene expression, and cell behaviour, in general, are affected by mechanical force application to the nucleus, which is transmitted from the cellular environment via a network of interconnected cytoskeletal components. To effectively regulate cell responses, these cytoskeletal components must not only exert forces but also withstand external forces when necessary. This review delves into the latest research concerning how the cytoskeleton safeguards the nucleus from mechanical perturbations. Specifically, we focus on the three primary cytoskeletal polymers: actin, intermediate filaments, and microtubules, as well as their interactions with the cell nucleus. We discuss how the cytoskeleton acts as a protective shield for the nucleus, ensuring structural integrity and conveying context-specific mechanoresponses.