Institute for Regenerative Medicine, Sechenov University, 119991 Moscow, Russia.
World-Class Research Center "Digital Biodesign and Personalized Healthcare", Sechenov University, 119991 Moscow, Russia.
Biochim Biophys Acta Gen Subj. 2023 Jun;1867(6):130348. doi: 10.1016/j.bbagen.2023.130348. Epub 2023 Mar 26.
Cytotoxicity assays are essential tests in studies on the safety and biocompatibility of various substances and on the efficiency of anticancer drugs. The most frequently used assays commonly require application of externally added labels and read only collective response of cells. Recent studies show that the internal biophysical parameters of cells can be associated with the cellular damage. Therefore, using atomic force microscopy, we assessed the changes in the viscoelastic parameters of cells treated with eight different common cytotoxic agents to gain a more systematic view of the occurring mechanical changes. With the robust statistical analysis to account for both the cell-level variability and the experimental reproducibility, we have found that cell softening is a common response after each treatment. More precisely, the combined changes in the viscoelastic parameters of power-law rheology model led to a significant decrease of the apparent elastic modulus. The comparison with the morphological parameters (cytoskeleton and cell shape) demonstrated a higher sensitivity of the mechanical parameters versus the morphological ones. The obtained results support the idea of cell mechanics-based cytotoxicity tests and suggest a common way of a cell responding to damaging actions by softening.
细胞毒性检测是研究各种物质的安全性和生物相容性以及抗癌药物效率的重要实验。最常用的检测方法通常需要外加标记物，并只能读取细胞的集体反应。最近的研究表明，细胞的内部生物物理参数可以与细胞损伤相关联。因此，我们使用原子力显微镜评估了八种不同常见细胞毒性剂处理后细胞的黏弹性参数变化，以更系统地了解发生的机械变化。通过稳健的统计分析，考虑到细胞水平的变异性和实验可重复性，我们发现每个处理后细胞变软是常见的反应。更准确地说，幂律流变学模型的黏弹性参数的综合变化导致表观弹性模量显著降低。与形态参数（细胞骨架和细胞形状）的比较表明，力学参数比形态参数更敏感。获得的结果支持基于细胞力学的细胞毒性检测的想法，并提出了细胞通过变软对损伤作用做出反应的常见方式。
