Abstract
Lamin A/C is a crucial player in nuclear properties and its alterations cause different diseases sharing some cellular features such as misshapen nuclei or premature senescence. If the impact of lamin A/C alterations is well described at the molecular and nuclear scales, notably on nuclear mechanics, their effects on cells and tissues need to be clarified. Here, we used a microfluidic device to force cells into constrictions and infer their mechanical properties. We benchmarked the mechanical response of whole cells and isolated nuclei from a healthy individual to that of prematurely senescent cells (i) affected by the lamin A/C R482W mutation associated to type-2 familial partial lipodystrophy (FPLD2), or treated by a protease inhibitor which alters lamin A/C production. We further challenged the cells with cytoskeletal drugs to destabilize the actin and microtubule networks. We found that senescent cells are more viscous than non-senescent ones, and that this change is not explained solely by mechanical changes in nuclei. Rather, we showed a major contribution from the cytoskeleton and uncovered an unexpected role of microtubules in prematurely senescent cells. These results suggest that lamin A/C not only impacts the nucleus but also its interplay with the cytoskeleton. By unveiling the enhanced cell viscosity as a marker of premature senescence, our study on cell mechanical properties paves the way towards a fast method for characterizing laminopathy-affected cells and testing drug therapy response.
Competing Interest Statement
The authors have declared no competing interest.