Cell nuclei as cytoplasmic rheometers

Cell nuclei as cytoplasmic rheometers
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细胞核作为细胞质流变仪

DOI:
10.1016/j.bpj.2021.02.030
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发表时间:
2021
影响因子:
3.4
通讯作者:
Schwarz, J.M.
Schwarz, J.M.
中科院分区:
生物学3区
文献类型:
--
作者:
Patteson, Alison E.;Schwarz, J.M.

文献摘要

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一些研究人员通过从外部干扰细胞来探测细胞的力学,例如使用原子力显微镜探头来记录细胞在以规定的速度施加规定的力时的变形量。其他研究人员通过从内部扰动细胞来探索细胞的力学,其中一个例子是粒子跟踪微观流变学,即早些时候弹道注入细胞内的亚微米被动荧光微珠的自发运动解码细胞模块。这两种类型的探头通常都是由非生物材料组成的。在这一期的《生物物理杂志》上,莫拉迪和纳佐克达斯巧妙地提出将细胞核本身作为细胞质机制的流变学探针(1)。细胞核通常是真核细胞中最大、最坚硬的细胞器。周围的细胞质包含其他细胞器和细胞骨架,细胞骨架由不同类型的半柔性聚合物组成,包括肌动蛋白、微管和中间丝。对于被限制在细胞大小尺度上的几何形状的细胞,细胞核变形最小,因此可以近似为刚性球体。正是在这个限度内,作者提出了以下问题。当细胞在微通道内运动时,细胞核的运动对细胞皮质的变形有何反应,揭示了细胞质的流变性?它是粘弹性的吗?它有渗透性吗?它是一个有孔洞弹性的网络吗?是不是还有别的事?对这些问题的回答将有助于我们更好地了解细胞功能,例如细胞质如何随着细胞物理环境的变化而重组。为了开始回答上述问题,作者关注了细胞膜下富含肌动蛋白和肌球蛋白的细胞皮质随时间的变形。这种变形将产生内部流动来驱动核运动,因为该模型假设细胞的某些外部体积包含牛顿流体。还存在粘弹性或孔弹性介质,例如,在细胞的某个内部体积内,以及细胞核心处的刚性球体或核(见图1)。注意,在这个框架内,不需要明确的细胞皮质机制。人们可以通过测量细胞核在细胞中移动的速度来推断细胞质的流变性,以响应皮质形状的变化。如果测得的细胞核速度随时间的变化与粘弹性流体的理论曲线一致,则可以认为细胞质是粘弹性流体。如果测量到的原子核速度是时间的函数
Some researchers probe the mechanics of cells by perturbing them from the outside, such as using an atomic force microscope probe to record the amount of deformation of the cell in response to applying a prescribed force at a defined speed. Other researchers probe the mechanics of cells by perturbing them from the inside, an example of which is particle-tracking microrheology, in which the spontaneous motion of submicron, passive fluorescent beads ballistically injected earlier into the cell decodes the cell moduli. Both types of probes are typically composed of nonliving material. In this issue of Biophysical Journal, Moradi and Nazockdas cleverly propose to use the cell nucleus itself as a rheological probe for the mechanics of the cytoplasm (1). The cell nucleus is typically the largest and the stiffest organelle in eukaryotic cells. The surrounding cytoplasm contains other organelles and the cytoskeleton, which is comprised different kinds of semiflexible polymers, including actin, microtubules, and intermediate filaments. For cells that are confined by geometries on the scale of the size of the cell, the nucleus is minimally deformed and can therefore be approximated as a rigid sphere. It is in this limit that the authors ask the following questions. As a cell moves inside a microchannel, what does the motion of the cell nucleus, in response to deformations in the cell cortex, reveal about the rheology of the cytoplasm? Is it viscoelastic? Is it porous? Is it a poroelastic network? Is it something else? Answers to such questions will help us better understand cell function, such as how the cytoplasm reorganizes in response to changes in a cell physical environment.To begin to answer the above questions, the authors focus on time-dependent deformations of the cell cortex, a regime rich with actin and myosin just beneath the cell membrane. Such deformations will generate internal flows to drive nuclear motion because the model assumes that some outer volume of the cell contains a Newtonian fluid. There also exists a viscoelastic or poroelastic medium, for example, within some inner volume of the cell, as well as a rigid sphere or the nucleus at the cell’s core (see Fig. 1). Note that within this framework, no explicit cell cortex mechanics is required. One can infer the rheological properties of the cell cytoplasm by measuring the velocity of the cell nucleus moving in the cell in response to the cortical shape change. If the measured velocity of the cell nucleus as a function of time agrees with the theoretical curve found for a viscoelastic fluid, then one can argue that the cytoplasm acts as a viscoelastic fluid. If the measured nucleus velocity as a function of time