Enhanced cell viscosity: a new phenotype associated with lamin A/C alterations

Cécile Jebane (1, 2) , Alice-Anaïs Varlet (3) , Marc Karnat (4, 2) , Lucero Hernandez- Cedillo (1, 2) , Amélie Lecchi (1) , Frédéric Bedu (1) , Camille Desgrouas (3) , Corinne Vigouroux (5, 6) , Marie-Christine Vantyghem (7) , Annie Viallat (1, 2) , Jean-François Rupprecht (4, 2) , Emmanuèle Helfer (1, 2) , Catherine Badens (8, 3)

1 CINaM - Centre Interdisciplinaire de Nanoscience de Marseille
2 TCLS - Turing Centre for Living Systems [Marseille]
3 MMG - Marseille medical genetics - Centre de génétique médicale de Marseille
4 CPT - Centre de Physique Théorique - UMR 7332
5 CHU Saint-Antoine [AP-HP]
6 CRSA - Centre de Recherche Saint-Antoine
7 RTD - Recherche translationnelle sur le diabète - U 1190
8 Département de Biochimie [Hôpital de la Timone - APHM]

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.

Mots clés: Lamin A/C; Lipodystrophy

Domaines: Biologie cellulaire; Physique [physics]; Matière Molle [cond-mat.soft]

Cécile Jebane, Alice-Anaïs Varlet, Marc Karnat, Lucero Hernandez- Cedillo, Amélie Lecchi, et al.. Enhanced cell viscosity: a new phenotype associated with lamin A/C alterations. iScience, 2023, 26 (10), pp.107714. ⟨10.1016/j.isci.2023.107714⟩. ⟨hal-04205177⟩