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首页> 外文期刊>Cell motility and the cytoskeleton >Mechanical dynamics of single cells during early apoptosis.
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Mechanical dynamics of single cells during early apoptosis.

机译:早期凋亡过程中单细胞的机械动力学。

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Dynamic mechanical properties of cells are becoming recognized as indicators and regulators of physiological processes such as differentiation, malignant phenotypes and mitosis. A key process in development and homeostasis is apoptosis and whilst the molecular control over this pathway is well studied, little is known about the mechanical consequences of cell death. Here, we study the caspase-dependent mechanical kinetics of single cells during early apoptosis initiated with the general protein-kinase inhibitor staurosporine. This results in internal remodelling of the cytoskeleton and nucleus which is reflected in dynamic changes in the mechanical properties of the cell. Utilizing simultaneous confocal and atomic force microscopy (AFM), we measured distinct mechanical dynamics in the instantaneous cellular Young's Modulus and longer timescale viscous deformation. This allowed us to visualize time-dependent nuclear and cytoskeletal control of force dissipation with fluorescent fusion proteins throughout the cell. This work reveals that the cell death program not only orchestrates biochemical dynamics but also controls the mechanical breakdown of the cell. Importantly, the consequences of mechanical disregulation during apoptosis may be a contributing factor to several human pathologies through the poorly timed release of dead cells and cell debris.
机译:细胞的动态力学性能已被视为生理过程(例如分化,恶性表型和有丝分裂)的指示剂和调节剂。发育和体内平衡的关键过程是细胞凋亡,尽管对该途径的分子控制进行了深入研究,但对细胞死亡的机械后果知之甚少。在这里,我们研究了由普通蛋白激酶抑制剂星形孢菌素引发的早期凋亡过程中单细胞的半胱天冬酶依赖性机械动力学。这导致细胞骨架和细胞核的内部重塑,这反映在细胞机械性质的动态变化中。利用同时共焦和原子力显微镜(AFM),我们在瞬时细胞杨氏模量和较长时间尺度的黏性变形中测量了不同的机械动力学。这使我们能够可视化荧光融合蛋白在整个细胞中对力消散的时间依赖性核和细胞骨架控制。这项工作表明,细胞死亡程序不仅可以协调生物化学动力学,还可以控制细胞的机械故障。重要的是,凋亡过程中机械失调的后果可能是由于死细胞和细胞碎片释放不及时而导致的几种人类病理的因素。

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