Affiliation:
1. Université Grenoble Alpes, Institute for Advanced Biosciences, Grenoble 38042, France
2. Paul Gerson Unna Group ‘Skin Homeostasis and Ageing’, Max Planck Institute for Biology of Ageing, Cologne 50931, Germany
3. Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne 50931, Germany
Abstract
ABSTRACT
Cells are constantly subjected to a spectrum of mechanical cues, such as shear stress, compression, differential tissue rigidity and strain, to which they adapt by engaging mechanisms of mechanotransduction. While the central role of cell adhesion receptors in this process is established, it has only recently been appreciated that mechanical cues reach far beyond the plasma membrane and the cytoskeleton, and are directly transmitted to the nucleus. Furthermore, changes in the mechanical properties of the perinuclear cytoskeleton, nuclear lamina and chromatin are critical for cellular responses and adaptation to external mechanical cues. In that respect, dynamic changes in the nuclear lamina and the surrounding cytoskeleton modify mechanical properties of the nucleus, thereby protecting genetic material from damage. The importance of this mechanism is highlighted by debilitating genetic diseases, termed laminopathies, that result from impaired mechanoresistance of the nuclear lamina. What has been less evident, and represents one of the exciting emerging concepts, is that chromatin itself is an active rheological element of the nucleus, which undergoes dynamic changes upon application of force, thereby facilitating cellular adaption to differential force environments. This Review aims to highlight these emerging concepts by discussing the latest literature in this area and by proposing an integrative model of cytoskeletal and chromatin-mediated responses to mechanical stress.
Funder
Max-Planck-Gesellschaft
Max Planck Förderstiftung
Deutsche Forschungsgemeinschaft
Whitaker International Fellows and Scholars Program
Horizon 2020 Framework Programme
Publisher
The Company of Biologists
Cited by
149 articles.
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