Biology subjects

Jebane, C.

Publications and source records attributed to Jebane, C..

2 recordsLinked to original sources

bioRxiv2022

Enhanced cell viscosity as a marker of premature senescence induced by lamin A/C alterations

Lamin A/C is a well-established key contributor to nuclear stiffness and its role in nucleus mechanical properties has been extensively studied. However, its impact on whole cell mechanics has been poorly addressed, even less so in terms of measurable physical parameters. In the present study, microfluidic experiments combined with theoretical analyses were performed to provide a quantitative estimation of the whole cell mechanical properties. This allowed the characterization of mechanical cell changes induced by lamin A/C alterations resulting from Atazanavir treatment or lipodystrophy-associated LMNA R482W pathogenic variant. Results unveil an increase in the long-time viscosity as a signature of cells affected by lamin A/C alterations. In addition, they 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. This enhanced cell viscosity assessed by our microfluidic device could represent a useful diagnosis marker for lamin-related diseases.

biophysics↗

bioRxiv2022

Mechanical stress driven by rigidity sensing governs epithelial stability

Epithelia act as a barrier against environmental stress and abrasion and in vivo they are continuously exposed to environments of various mechanical properties. The impact of this environment on epithelial integrity remains elusive. By culturing epithelial cells on 2D hydrogels, we observe a loss of epithelial monolayer integrity through spontaneous hole formation when grown on soft substrates. Substrate stiffness triggers an unanticipated mechanical switch of epithelial monolayers from tensile on soft to compressive on stiff substrates. Through active nematic modelling, we find unique patterns of cell shape texture called nematic topological defects that underpin large isotropic stress fluctuations at certain locations thereby triggering mechanical failure of the monolayer and hole opening. Our results show that substrate stiffness provides feedback on monolayer mechanical state and that topological defects can trigger stochastic mechanical failure, with potential application towards a mechanistic understanding of compromised epithelial integrity in bacterial infection, tumor progression and morphogenesis.

biophysics↗