ИСТИНА

The nuclear lamina (NL) is the main rigid component of the cell nucleus. The NL consists of a meshwork of intermediate filaments built from lamins of A- and B-types of which lamin A plays a crucial role in cell migration, proliferation, DNA repair, cell death, etc. Mutations in the lamin A gene cause many diseases, from myodystrophies, lipodystrophies, neuropathies to premature aging. The mechanisms which underlie such severe phenotypes are still unclear. The present work aimed to estimate the effect of poorly studied missense mutations of lamin A - R527P and R249Q on the morphology and mechanical properties of the cell. We evaluated the lamin A meshwork morphology in normal HT1080 cells and cells expressing mutant lamins A genes with fluorescent microscopy. We showed local disarrangement of the NL and nuclear asymmetry. Also, we found the formation of lamin A aggregates as part of the NL. Then, we measured cellular stiffness using scanning ion-conducting microscopy. We compared the elastic modulus in the central part and periphery of cells and found that the cell nucleus displays higher stiffness than the cytoplasm. Also, the mutant cells were found to be ∼1.6 times more rigid relative to wild-type cells.