MiMEtiC · Molecular mechanisms of the mechanical interaction between the cell nucleus and the actin cytoskeleton

Molecular mechanisms of the mechanical interaction between the cell nucleus and the actin cytoskeleton

Cell survival and tissue integrity depend on the ability to maintain structural and functional integrity even under conditions of stress. Cells are constantly exposed to dynamic changes in their physical microenvironment, and these mechanical forces is a source of physiologically and clinically relevant stress. Mechanical stress protection operates during cell differentiation, adhesion and migration, and is of particular importance for maintaining tissues such as skeletal muscle, heart, lung, vasculature, and skin. Yet, underlying molecular mechanisms have not been comprehensively studied. However, what is already obvious is that impairment mechanical stress protection and/or mechanoadaptation processes gives rise to diverse diseases, including myopathies, heart and kidney failure, leukocyte adhesion deficiencies, progeroid diseases and cancer. Thus, there is a critical research need for detailed molecular understanding of mechanical stress responses in order to design diagnostic tools and therapeutic interventions. Epithelial tissues such as the skin epidermis are critical load-bearing elements of the body. They undergo large-scale, force-driven deformations during morphogenesis and in the adult organism. Strikingly, in contrast to cancer cells where mechanical deformations have been shown to induce nuclear rupture and DNA damage, such effects have not been observed in untransformed epithelial cells. On the contrary, epithelial cells have been shown to be capable of undergoing extreme deformation without damage, and to withstand long-term mechanical strain without signs of genomic damage or loss of viability. This project aimed to understand how nuclei respond to mechanical stress and how the genome is protected under extreme nuclear deformations

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз