研究动态
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癌细胞的机械显微镜研究:TGF-β引发的上皮向间质转化对应于癌细胞内较低的细胞内粘度。

Mechanical microscopy of cancer cells: TGF-β induced epithelial to mesenchymal transition corresponds to low intracellular viscosity in cancer cells.

发表日期:2023 Sep 01
作者: Diplesh Gautam, Abhilasha Srivastava, Rajdeep Chowdhury, Inamur R Laskar, Venkatesh K P Rao, Sudeshna Mukherjee
来源: CYTOKINE & GROWTH FACTOR REVIEWS

摘要:

黏度是调节扩散驱动的细胞过程中生物分子反应速率的重要参数。因此,异常的黏度水平通常与各种疾病和功能障碍(如癌症)相关联。因此,监测细胞内黏度变得至关重要。虽然已经开发了几种用于体外和体内测量黏度的方法,但对活体细胞内黏度的分析尚未得到很好的实现。我们的研究引入了一种新颖的基于固有频率的非侵入性方法,用于确定细胞内黏度。这种方法不仅可以有效地分析PEG或葡萄糖等分子调节后细胞内黏度的差异,而且还足够敏感,可以区分Huh-7、MCF-7和MDAMB-231等各种癌细胞系之间的细胞内黏度差异。有趣的是,细胞因子TGF-β被报道能够诱导上皮向间充质转化(EMT),这是与癌症浸润相关的特征,但通过我们的方法捕获到TGF-β使癌细胞黏度降低。为了验证我们的发现与现有分析方法的一致性,我们使用了之前描述的黏度敏感的分子转子荧光团-TPSII来分析细胞内黏度。与我们的位置传感器装置(PSD)方法一致,黏度增强剂导致荧光强度增加,而TGF-β暴露导致细胞中荧光强度降低。这是首个尝试使用新颖的非侵入性PSD方法表征细胞内黏度差异的研究。© 2023 Acoustical Society of America.
Viscosity is an essential parameter that regulates bio-molecular reaction rates of diffusion-driven cellular processes. Hence, abnormal viscosity levels are often associated with various diseases and malfunctions like cancer. For this reason, monitoring intracellular viscosity becomes vital. While several approaches have been developed for in vitro and in vivo measurement of viscosity, analysis of intracellular viscosity in live cells has not yet been well realized. Our research introduces a novel, natural frequency-based, non-invasive method to determine the intracellular viscosity in cells. This method can not only efficiently analyze the differences in intracellular viscosity post modulation with molecules like PEG or glucose but is sensitive enough to distinguish the difference in intra-cellular viscosity among various cancer cell lines such as Huh-7, MCF-7, and MDAMB-231. Interestingly, TGF-β a cytokine reported to induce epithelial to mesenchymal transition (EMT), a feature associated with cancer invasiveness resulted in reduced viscosity of cancer cells, as captured through our method. To corroborate our findings with existing methods of analysis, we analyzed intra-cellular viscosity with a previously described viscosity-sensitive molecular rotor-based fluorophore-TPSII. In parity with our position sensing device (PSD)-based approach, an increase in fluorescence intensity was observed with viscosity enhancers, while, TGF-β exposure resulted in its reduction in the cells studied. This is the first study of its kind that attempts to characterize differences in intracellular viscosity using a novel, non-invasive PSD-based method.© 2023 Acoustical Society of America.