Micro-Nano Biomechanics Laboratory, Department of Mechanical Systems Engineering, Ibaraki University, Nakanarusawa-cho, Hitachi, 316-8511, Japan.
Micro-Nano Biomechanics Laboratory, Department of Mechanical Systems Engineering, Ibaraki University, Nakanarusawa-cho, Hitachi, 316-8511, Japan.
J Mech Behav Biomed Mater. 2024 Aug;156:106586. doi: 10.1016/j.jmbbm.2024.106586. Epub 2024 May 22.
Both mechanical and adhesion properties of cancer cells are complex and reciprocally related to migration, invasion, and metastasis with large cell deformation. Therefore, we evaluated these properties for human cervical cancer cells (HeLa) simultaneously using our previously developed micro tensile tester system. For efficient evaluation, we developed image analysis software to modify the system. The software can analyze the tensile force in real time. The modified system can evaluate the tensile stiffness of cells to which a large deformation is applied, also evaluate the adhesion strength of cancer cells that adhered to a culture substrate and were cultured for several days with their adhesion maturation. We used the modified system to simultaneously evaluate the stiffness of the cancer cells to which a large deformation was applied and their adhesion strength. The obtained results revealed that the middle phase of tensile stiffness and adhesion force of the microtubule-depolymerized group treated with colchicine (an anti-cancer drug) (stiffness, 13.4 ± 7.5 nN/%; adhesion force, 460.6 ± 258.2 nN) were over two times larger than those of the control group (stiffness, 5.0 ± 3.5 nN/%; adhesion force, 168.2 ± 98.0 nN). Additionally, the same trend was confirmed with the detailed evaluation of cell surface stiffness using an atomic force microscope. Confocal fluorescence microscope observations showed that the stress fibers (SFs) of colchicine-treated cells were aligned in the same direction, and focal adhesions (FAs) of the cells developed around both ends of the SFs and aligned parallel to the developed direction of the SFs. There was a possibility that the microtubule depolymerization by the colchicine treatment induced the development of SFs and FAs and subsequently caused an increment of cell stiffness and adhesion force. From the above results, we concluded the modified system would be applicable to cancer detection and anti-cancer drug efficacy tests.
癌细胞的力学和黏附特性非常复杂，与大细胞变形相关，并相互影响迁移、侵袭和转移。因此，我们使用之前开发的微拉伸测试仪系统同时评估了人宫颈癌细胞（HeLa）的这些特性。为了进行有效的评估，我们开发了图像分析软件来修改系统。该软件可以实时分析拉伸力。修改后的系统可以评估应用大变形的细胞的拉伸刚度，还可以评估已附着在培养基板上并经过数天附着成熟的癌细胞的粘附强度。我们使用修改后的系统同时评估了应用大变形的癌细胞的刚度及其粘附强度。获得的结果表明，秋水仙碱（抗癌药物）处理的微管去聚合组的拉伸刚度中间相和粘附力（刚度 13.4 ± 7.5 nN/%；粘附力 460.6 ± 258.2 nN）超过对照组的两倍（刚度 5.0 ± 3.5 nN/%；粘附力 168.2 ± 98.0 nN）。此外，使用原子力显微镜对细胞表面刚度进行详细评估，也证实了相同的趋势。共聚焦荧光显微镜观察表明，秋水仙碱处理的细胞中的应力纤维（SFs）沿相同方向排列，并且细胞的焦点粘连（FAs）沿着 SFs 的两端发展并与 SFs 的发展方向平行排列。秋水仙碱处理导致微管去聚合，可能会诱导 SFs 和 FAs 的发展，从而导致细胞刚度和粘附力增加。根据上述结果，我们得出结论，修改后的系统将适用于癌症检测和抗癌药物疗效测试。
