Jebane Cécile, Varlet Alice-Anaïs, Karnat Marc, Hernandez-Cedillo Lucero M, Lecchi Amélie, Bedu Frédéric, Desgrouas Camille, Vigouroux Corinne, Vantyghem Marie-Christine, Viallat Annie, Rupprecht Jean-François, Helfer Emmanuèle, Badens Catherine
Aix Marseille Univ, CNRS, CINAM, Turing Centre for Living Systems, Marseille, France.
Aix Marseille Univ, INSERM, MMG, Marseille, France.
iScience. 2023 Aug 25;26(10):107714. doi: 10.1016/j.isci.2023.107714. eCollection 2023 Oct 20.
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.
核纤层蛋白A/C是核硬度公认的关键促成因素，其在细胞核力学特性中的作用已得到广泛研究。然而，其对全细胞力学的影响却很少被提及，尤其是在可测量的物理参数方面。在本研究中，我们将微流控实验与理论分析相结合，以定量评估全细胞的力学特性。这使我们能够表征由阿扎那韦治疗或脂肪营养不良相关的LMNA R482W致病变体引起的核纤层蛋白A/C改变和前体核纤层蛋白A积累在细胞中诱导的力学变化。我们的结果揭示了长时间粘度的显著增加，这是受核纤层蛋白A/C改变影响的细胞的一个特征。此外，结果表明，全细胞对机械应力的反应不仅由细胞核驱动，还由核-细胞骨架连接和微管网络驱动。通过我们的微流控测定法评估的细胞粘度增加，可作为层粘连蛋白相关疾病的有价值诊断标志物。
