A high throughput approach for analysis of cell nuclear deformability at single cell level.

A high throughput approach for analysis of cell nuclear deformability at single cell level.
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一种高通量方法,用于分析单细胞水平的细胞核可变形性。

DOI:
10.1038/srep36917
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发表时间:
2016-11-14
期刊:
影响因子:
4.6
通讯作者:
Hasirci V
Hasirci V
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Ermis M;Akkaynak D;Chen P;Demirci U;Hasirci V

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细胞分化、迁移、附着和转移等各种生理和病理过程高度依赖于核弹性。核形态直接反映了细胞核的弹性。我们建议,对具有确定形貌的表面上的核形态变化进行量化将使我们能够评估核弹性和可变形性。在这里,我们使用软光刻技术来生产 3 维 (3-D) 细胞培养基质,其装饰有可变纵横比和尺寸的微米级柱结构,以诱导细胞和核形态的变化。我们开发了一种高内涵图像分析算法,用于量化单细胞水平上核形态的变化,以响应来自 3D 培养基质的物理线索。我们提出,核硬度可以用作物理参数,根据癌细胞的谱系并与源自相同组织类型的非癌细胞进行比较来评估癌细胞。该方法可用于系统研究大细胞群的机械特性,以补充原子力显微镜和纳米压痕等传统工具。
Various physiological and pathological processes, such as cell differentiation, migration, attachment, and metastasis are highly dependent on nuclear elasticity. Nuclear morphology directly reflects the elasticity of the nucleus. We propose that quantification of changes in nuclear morphology on surfaces with defined topography will enable us to assess nuclear elasticity and deformability. Here, we used soft lithography techniques to produce 3 dimensional (3-D) cell culture substrates decorated with micron sized pillar structures of variable aspect ratios and dimensions to induce changes in cellular and nuclear morphology. We developed a high content image analysis algorithm to quantify changes in nuclear morphology at the single-cell level in response to physical cues from the 3-D culture substrate. We present that nuclear stiffness can be used as a physical parameter to evaluate cancer cells based on their lineage and in comparison to non-cancerous cells originating from the same tissue type. This methodology can be exploited for systematic study of mechanical characteristics of large cell populations complementing conventional tools such as atomic force microscopy and nanoindentation.
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