Cell mechanics upon lamin A/C alterations

Lamin A/C is a crucial component of the nucleus and the impact of lamin A/C alterations has been extensively described at the molecular and nuclear scales, notably on nucleus mechanical properties. However, its impact on whole-cell mechanics has been poorly addressed, even less so in terms of measurable physical parameters.

In the present study, we combined microfluidic experiments with theoretical analyses to provide a quantitative estimation of the whole-cell mechanical properties. This allowed us to characterize the mechanical changes induced in cells by lamin A/C alterations resulting either from Atazanavir treatment, a protease inhibitor which alters lamin A/C production, or from lamin A/C R482W mutation associated to type-2 familial partial lipodystrophy (FPLD2).

We reveal a distinctive increase in long-time viscosity as a signature of cells affected by lamin A/C alterations. Furthermore, our results show that the whole-cell response to mechanical stress is driven not only by the nucleus but also by the nucleo-cytoskeleton links and the microtubule network. The enhanced cell viscosity assessed by our microfluidic assay could serve as a valuable diagnosis marker for lamin-related diseases.