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

Cécile Jebane; Alice-Anaïs Varlet; Marc Karnat; Lucero M Hernandez-Cedillo; Amélie Lecchi; Frédéric Bedu; Camille Desgrouas; Corinne Vigouroux; Marie-Christine Vantyghem; Annie Viallat; Jean-François Rupprecht; Emmanuèle Helfer; Catherine Badens

doi:10.1016/j.isci.2023.107714

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

iScience. 2023 Aug 25;26(10):107714. doi: 10.1016/j.isci.2023.107714. eCollection 2023 Oct 20.

Authors

Affiliations

¹ Aix Marseille Univ, CNRS, CINAM, Turing Centre for Living Systems, Marseille, France.
² Aix Marseille Univ, INSERM, MMG, Marseille, France.
³ Aix Marseille Univ, Université de Toulon, CNRS, CPT, Turing Centre for Living Systems, Marseille, France.
⁴ Aix Marseille Univ, CNRS, CINAM, Marseille, France.
⁵ Assistance Publique-Hôpitaux de Paris (AP-HP), Saint-Antoine Hospital, National Reference Centre for Rares diseases of Insulin-Secretion and Insulin-Sensitivity (PRISIS), Department of Endocrinology, Paris, France.
⁶ Sorbonne University, Saint-Antoine Research Centre, Inserm UMR_S938, Institute of Cardiometabolism and Nutrition, Paris, France.
⁷ Endocrinology, Diabetology and Metabolism Department, Inserm U1190, EGID, Lille University Hospital, Lille, France.
⁸ AP-HM, Laboratoire de Biochimie, Marseille, France.

Abstract

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, particularly concerning measurable physical parameters. In this study, we combined microfluidic experiments with theoretical analyses to quantitatively estimate the whole-cell mechanical properties. This allowed us to characterize the mechanical changes induced in cells by lamin A/C alterations and prelamin A accumulation resulting from atazanavir treatment or lipodystrophy-associated LMNA R482W pathogenic variant. Our results reveal a distinctive increase in long-time viscosity as a signature of cells affected by lamin A/C alterations. Furthermore, 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. The enhanced cell viscosity assessed with our microfluidic assay could serve as a valuable diagnosis marker for lamin-related diseases.

Keywords: Biological sciences; Biotechnology; Cell biology.