Molecular and Clinical Sciences Research Institute, St George's, University of London, London SW17 0RE, UK.
Department of Medicine, Imperial College London, W12 0NN London, UK.
Cells. 2023 Oct 4;12(19):2401. doi: 10.3390/cells12192401.
A cell's mechanical properties have been linked to cancer development, motility and metastasis and are therefore an attractive target as a universal, reliable cancer marker. For example, it has been widely published that cancer cells show a lower Young's modulus than their non-cancerous counterparts. Furthermore, the effect of anti-cancer drugs on cellular mechanics may offer a new insight into secondary mechanisms of action and drug efficiency. Scanning ion conductance microscopy (SICM) offers a nanoscale resolution, non-contact method of nanomechanical data acquisition. In this study, we used SICM to measure the nanomechanical properties of melanoma cell lines from different stages with increasing metastatic ability. Young's modulus changes following treatment with the anti-cancer drugs paclitaxel, cisplatin and dacarbazine were also measured, offering a novel perspective through the use of continuous scan mode SICM. We found that Young's modulus was inversely correlated to metastatic ability in melanoma cell lines from radial growth, vertical growth and metastatic phases. However, Young's modulus was found to be highly variable between cells and cell lines. For example, the highly metastatic cell line A375M was found to have a significantly higher Young's modulus, and this was attributed to a higher level of F-actin. Furthermore, our data following nanomechanical changes after 24 hour anti-cancer drug treatment showed that paclitaxel and cisplatin treatment significantly increased Young's modulus, attributed to an increase in microtubules. Treatment with dacarbazine saw a decrease in Young's modulus with a significantly lower F-actin corrected total cell fluorescence. Our data offer a new perspective on nanomechanical changes following drug treatment, which may be an overlooked effect. This work also highlights variations in cell nanomechanical properties between previous studies, cancer cell lines and cancer types and questions the usefulness of using nanomechanics as a diagnostic or prognostic tool.
细胞的力学特性与癌症的发生、运动和转移有关，因此作为一种普遍、可靠的癌症标志物，具有吸引力。例如，广泛发表的研究表明，癌细胞的杨氏模量低于非癌性细胞。此外，抗癌药物对细胞力学的影响可能为作用机制和药物效率的新见解提供新的见解。扫描离子电导显微镜（SICM）提供了纳米级分辨率、非接触式纳米力学数据采集方法。在这项研究中，我们使用 SICM 测量了具有不同转移能力的不同阶段黑色素瘤细胞系的纳米力学特性。还测量了抗癌药物紫杉醇、顺铂和达卡巴嗪处理后杨氏模量的变化，通过使用连续扫描模式 SICM 提供了新的视角。我们发现，杨氏模量与黑色素瘤细胞系的转移能力呈负相关，从辐射生长、垂直生长和转移阶段。然而，杨氏模量在细胞和细胞系之间发现高度可变。例如，高度转移性细胞系 A375M 被发现具有明显更高的杨氏模量，这归因于更高水平的 F-肌动蛋白。此外，我们在抗癌药物治疗 24 小时后纳米力学变化的数据表明，紫杉醇和顺铂处理显著增加了杨氏模量，这归因于微管的增加。达卡巴嗪处理导致杨氏模量降低，F-肌动蛋白校正的总细胞荧光显著降低。我们的数据提供了药物治疗后纳米力学变化的新视角，这可能是一个被忽视的影响。这项工作还突出了先前研究、癌细胞系和癌症类型之间细胞纳米力学特性的差异，并质疑将纳米力学用作诊断或预后工具的有用性。
