Multimodal microscale mechanical mapping of cancer cells in complex microenvironments
Multimodal microscale mechanical mapping of cancer cells in complex microenvironments
复制标题
复杂微环境中癌细胞的多模态微尺度机械测绘
DOI：
10.1016/j.bpj.2022.09.002
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发表时间：
2022
影响因子：
3.4
通讯作者：
Tanner, Kandice
中科院分区：
文献类型：
--
作者：
Nikolić, Miloš;Scarcelli, Giuliano;Tanner, Kandice
细胞的机械表型对于因限制和流体流动而变形后的存活至关重要。一种想法是癌细胞是可塑性的，在不同的几何形状下采用不同的机械表型，这有助于它们的生存。因此，一个有吸引力的目标是破坏癌细胞采用多种机械状态的能力。为了开始解决这个问题，我们的目标是使用体外仿生技术在体内二维(2D)和3D细胞外基质环境中模拟这些机械状态的多样性。在这里，我们使用了两种模式的布里渊显微镜(∼GHz)和宽带频率(7-15 KHz)的光钳微观流变学来测量微尺度的细胞力学。我们测量了在2D和3D环境中培养的癌细胞的细胞内力学反应，在这些环境中，我们改变了底物硬度、维度(2D与3D)和纤维形态的存在。我们确定，尽管两种测量的时间尺度不同，但两种模式之间有很好的一致性。这些关于不同环境中细胞机械表型的发现证实了在不同时间尺度(赫兹-千赫与吉赫)采用不同机制的模式之间的相关性。我们还确定，观察到的细胞形状的异质性与细胞的机械状态更紧密地联系在一起。此外，与单分散3D培养中的单个细胞相比，多细胞球体中的单个细胞表现出较低程度的机械异质性。观察到球体中细胞之间的异质性降低，这表明组成单个球体的细胞之间存在机械协作性。
The mechanical phenotype of the cell is critical for survival following deformations due to confinement and fluid flow. One idea is that cancer cells are plastic and adopt different mechanical phenotypes under different geometries that aid in their survival. Thus, an attractive goal is to disrupt cancer cells' ability to adopt multiple mechanical states. To begin to address this question, we aimed to quantify the diversity of these mechanical states using in vitro biomimetics to mimic in vivo two-dimensional (2D) and 3D extracellular matrix environments. Here, we used two modalities Brillouin microscopy (∼GHz) and broadband frequency (7–15 kHz) optical tweezer microrheology to measure microscale cell mechanics. We measured the response of intracellular mechanics of cancer cells cultured in 2D and 3D environments where we modified substrate stiffness, dimensionality (2D versus 3D), and presence of fibrillar topography. We determined that there was good agreement between two modalities despite the difference in timescale of the two measurements. These findings on cell mechanical phenotype in different environments confirm a correlation between modalities that employ different mechanisms at different temporal scales (Hz-kHz versus GHz). We also determined that observed heterogeneity in cell shape is more closely linked to the cells' mechanical state. Moreover, individual cells in multicellular spheroids exhibit a lower degree of mechanical heterogeneity when compared with single cells cultured in monodisperse 3D cultures. The observed decreased heterogeneity among cells in spheroids suggested that there is mechanical cooperativity between cells that make up a single spheroid.
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影响因子：
11.2
作者：
Ulrich TA;de Juan Pardo EM;Kumar S
通讯作者：
Kumar S
DOI：
10.1101/232066
发表时间：
2017
期刊：
bioRxiv
影响因子：
--
作者：
C. Paul;Alex M. Hruska;J. Staunton;Hannah A. Burr;Jiyun Kim;N. Jiang;K. Tanner
通讯作者：
K. Tanner
影响因子：
19
作者：
Huh, Dongeun;Hamilton, Geraldine A.;Ingber, Donald E.
通讯作者：
Ingber, Donald E.
影响因子：
4.8
作者：
Debnath, J;Muthuswamy, SK;Brugge, JS
通讯作者：
Brugge, JS
影响因子：
13.6
作者：
Wisniewski, Emily O.;Mistriotis, Panagiotis;Konstantopoulos, Konstantinos
通讯作者：
Konstantopoulos, Konstantinos