Mechanical, nanomorphological and biological reconstruction of early-stage apoptosis in HeLa cells induced by cytochalasin B

Mechanical, nanomorphological and biological reconstruction of early-stage apoptosis in HeLa cells induced by cytochalasin B
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细胞松弛素 B 诱导的 HeLa 细胞早期凋亡的机械、纳米形态和生物学重建

DOI:
10.3892/or.2018.6921
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发表时间:
2019-02-01
期刊:
影响因子:
4.2
通讯作者:
Wang,Jizeng
Wang,Jizeng
中科院分区:
医学3区
文献类型:
--
作者:
Su,Xuelian;Zhang,Ling;Wang,Jizeng

文献摘要

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人们越来越感兴趣的是,在评估细胞活力方面,机械信号可能与生物信号一样重要。为了研究早期细胞凋亡过程中生物力学、纳米形态和生物凋亡信号的变化,建立了细胞松弛素B(CB)诱导的宫颈癌HeLa细胞凋亡模型。系统分析了细胞的力学特性、几何形状、形态和关键凋亡蛋白的表达。研究结果表明,在生物凋亡信号激活(例如磷脂酰丝氨酸暴露或 CD95/Fas 激活)之前,细胞弹性模量和体积显着下降,表面粗糙度显着增加。此外,丝状肌动蛋白的解聚加剧了细胞内的拥挤程度,从而导致不同大小的蛋白质分子重新分布,并由于排除的体积相互作用而在细胞膜上形成突起。统计分析显示,肌动蛋白细胞骨架的分解与细胞弹性模量和体积呈负相关,而与表面粗糙度和CD95/Fas活化呈正相关。本研究结果表明,与生物信号相比,机械和几何重建在细胞凋亡过程中更为敏感,细胞表面粗糙度的增加源于生物物理分子的重新分布。这些结果有助于我们深入了解细胞松弛素B介导的癌细胞凋亡机制。
There is a growing interest in the fact that mechanical signals may be as important as biological signals in evaluating cell viability. To investigate the alterations in biomechanics, nanomorphology and biological apoptotic signals during early apoptosis, an apoptosis model was established for cervical cancer HeLa cells induced by cytochalasin B (CB). The cellular mechanical properties, geometry, morphology and expression of key apoptotic proteins were systematically analyzed. The findings indicated a marked decline in cellular elastic modulus and volume and a considerable increase in surface roughness occurring prior to the activation of biological apoptosis signals (such as phosphatidylserine exposure or activation of CD95/Fas). Moreover, the depolymerization of filamentous actin aggravated the intracellular crowding degree, which induced the redistribution of different-sized protein molecules and protrusions across the cell membrane arising from excluded volume interactions. Statistical analysis revealed that the disassembly of the actin cytoskeleton was negatively correlated with the cellular elastic modulus and volume, but was positively correlated with surface roughness and CD95/Fas activation. The results of the present study suggest that compared with biological signals, mechanical and geometrical reconstruction is more sensitive during apoptosis and the increase in cell surface roughness arises from the redistribution of biophysical molecules. These results contribute to our in-depth understanding of the apoptosis mechanisms of cancer cells mediated by cytochalasin B.