BioSystems Science and Engineering, Indian Institute of Science, Bengaluru, Karnataka, India.
Mechanical Engineering, Indian Institute of Science, Bengaluru, Karnataka, India.
Biophys J. 2019 Apr 2;116(7):1328-1339. doi: 10.1016/j.bpj.2019.02.013. Epub 2019 Feb 26.
Morphology of the nucleus is an important regulator of gene expression. Nuclear morphology is in turn a function of the forces acting on it and the mechanical properties of the nuclear envelope. Here, we present a two-parameter, nondimensional mechanical model of the nucleus that reveals a relationship among nuclear shape parameters, such as projected area, surface area, and volume. Our model fits the morphology of individual nuclei and predicts the ratio between forces and modulus in each nucleus. We analyzed the changes in nuclear morphology of liver cells due to hepatitis C virus (HCV) infection using this model. The model predicted a decrease in the elastic modulus of the nuclear envelope and an increase in the pre-tension in cortical actin as the causes for the change in nuclear morphology. These predictions were validated biomechanically by showing that liver cells expressing HCV proteins possessed enhanced cellular stiffness and reduced nuclear stiffness. Concomitantly, cells expressing HCV proteins showed downregulation of lamin-A,C and upregulation of β-actin, corroborating the predictions of the model. Our modeling assumptions are broadly applicable to adherent, monolayer cell cultures, making the model amenable to investigate changes in nuclear mechanics due to other stimuli by merely measuring nuclear morphology. Toward this, we present two techniques, graphical and numerical, to use our model for predicting physical changes in the nucleus.
核的形态是基因表达的一个重要调节因子。核的形态又是作用于核的力和核膜的力学性能的函数。在这里，我们提出了一个双参数、无量纲的核力学模型，揭示了核的形状参数（如投影面积、表面积和体积）之间的关系。我们的模型适合于单个核的形态，并预测了每个核中的力和模量之间的比值。我们使用该模型分析了丙型肝炎病毒（HCV）感染导致的肝细胞核形态变化。该模型预测，核膜的弹性模量降低和皮质肌动蛋白的预张力增加是核形态变化的原因。通过证明表达 HCV 蛋白的肝细胞具有增强的细胞刚性和降低的核刚性，从生物力学上验证了这些预测。同时，表达 HCV 蛋白的细胞表现出核纤层蛋白 A、C 的下调和β-肌动蛋白的上调，这与模型的预测结果相符。我们的建模假设广泛适用于贴壁单层细胞培养物，使得该模型可以通过测量核形态来研究由于其他刺激而导致的核力学变化。为此，我们提出了两种技术，即图形和数值技术，用于使用我们的模型来预测核内的物理变化。
