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Inertial picobalance reveals fast mass fluctuations in mammalian cells

机译：惯性微微平衡揭示哺乳动物细胞中快速的质量波动

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摘要

The regulation of size, volume and mass in living cells is physiologically important, and dysregulation of these parameters gives rise to many diseases(1). Cell mass is largely determined by the amount of water, proteins, lipids, carbohydrates and nucleic acids present in a cell, and is tightly linked to metabolism, proliferation(2) and gene expression(3). Technologies have emerged in recent years that make it possible to track the masses of single suspended cells(4,5) and adherent cells(6-8). However, it has not been possible to track individual adherent cells in physiological conditions at the mass and time resolutions required to observe fast cellular dynamics. Here we introduce a cell balance (a 'picobalance'), based on an optically excited microresonator, that measures the total mass of single or multiple adherent cells in culture conditions over days with millisecond time resolution and picogram mass sensitivity. Using our technique, we observe that the mass of living mammalian cells fluctuates intrinsically by around one to four per cent over timescales of seconds throughout the cell cycle. Perturbation experiments link these mass fluctuations to the basic cellular processes of ATP synthesis and water transport. Furthermore, we show that growth and cell cycle progression are arrested in cells infected with vaccinia virus, but mass fluctuations continue until cell death. Our measurements suggest that all living cells show fast and subtle mass fluctuations throughout the cell cycle. As our cell balance is easy to handle and compatible with fluorescence microscopy, we anticipate that our approach will contribute to the understanding of cell mass regulation in various cell states and across timescales, which is important in areas including physiology, cancer research, stem-cell differentiation and drug discovery.
机译：活细胞大小，体积和质量的调节在生理上很重要，而这些参数的失调会引起许多疾病（1）。细胞质量很大程度上取决于细胞中存在的水，蛋白质，脂质，碳水化合物和核酸的量，并且与代谢，增殖（2）和基因表达（3）紧密相关。近年来出现的技术使得跟踪单个悬浮细胞（4,5）和贴壁细胞（6-8）的质量成为可能。但是，不可能在生理条件下以观察快速细胞动力学所需的质量和时间分辨率来追踪单个贴壁细胞。在此，我们介绍一种基于光激发微谐振器的细胞平衡（“微微平衡”），该平衡可在几天内以毫秒级的时间分辨率和皮克质量灵敏度来测量培养条件下单个或多个贴壁细胞的总质量。使用我们的技术，我们观察到在整个细胞周期内，哺乳动物活动细胞的质量在几秒钟内随时间波动约1-4％。摄动实验将这些质量波动与ATP合成和水传输的基本细胞过程联系起来。此外，我们表明生长和细胞周期进程被牛痘病毒感染的细胞中止，但质量波动持续到细胞死亡。我们的测量结果表明，所有活细胞在整个细胞周期中均显示出快速而细微的质量波动。由于我们的细胞平衡易于处理且与荧光显微镜兼容，因此我们预计我们的方法将有助于理解各种细胞状态和跨时间尺度的细胞质量调节，这在生理学，癌症研究，干细胞等领域非常重要分化和药物发现。

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  • 来源
    《Nature》 |2017年第7677期|500-505|共6页
  • 作者

    Martinez-Martin David; Flaschner Gotthold; Gaub Benjamin; Martin Sascha; Newton Richard; Beerli Corina; Mercer Jason; Gerber Christoph; Mueller Daniel J.;

  • 作者单位

    Eidgenoss Tech Hsch ETH Zurich, Dept Biosyst Sci & Engn, CH-4058 Basel, Switzerland;

    Eidgenoss Tech Hsch ETH Zurich, Dept Biosyst Sci & Engn, CH-4058 Basel, Switzerland;

    Eidgenoss Tech Hsch ETH Zurich, Dept Biosyst Sci & Engn, CH-4058 Basel, Switzerland;

    Univ Basel, Swiss Nanosci Inst, CH-4056 Basel, Switzerland;

    Eidgenoss Tech Hsch ETH Zurich, Dept Biosyst Sci & Engn, CH-4058 Basel, Switzerland;

    UCL, MRC Lab Mol Cell Biol, London WC1E 6BT, England;

    UCL, MRC Lab Mol Cell Biol, London WC1E 6BT, England;

    Univ Basel, Swiss Nanosci Inst, CH-4056 Basel, Switzerland;

    Eidgenoss Tech Hsch ETH Zurich, Dept Biosyst Sci & Engn, CH-4058 Basel, Switzerland;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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