Gradient-on-a-Chip with Reactive Oxygen Species Reveals Thresholds in the Nucleus Response of Cancer Cells Depending on the Matrix Environment
Gradient-on-a-Chip with Reactive Oxygen Species Reveals Thresholds in the Nucleus Response of Cancer Cells Depending on the Matrix Environment
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DOI：
10.1021/acsbiomaterials.7b00087
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发表时间：
2018-02-01
影响因子：
5.8
通讯作者：
Lelievre, Sophie A.
中科院分区：
文献类型：
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作者：
Chittiboyina, Shirisha;Rahimi, Rahim;Lelievre, Sophie A.
氧化应激介导的癌症进展取决于细胞外基质（ECM）中活性氧（ROS）的暴露。为了研究 ROS 水平对浸润前乳腺癌细胞的影响作为 ECM 特征的函数，我们创建了一个芯片梯度，其中 H2O2 逐渐与相连微通道内的细胞培养基混合，并向上扩散到开放细胞培养窗口的 ECM 中。该装置利用纸基微流体分叉混合器插入物来防止泄漏并有利于均匀的流体分布。通过测量催化成氧气的 H2O2 来确认梯度，并在 2D 和基于 ECM 的 3D 细胞培养物中记录增加的氧化 DNA 损伤和保护性 (AOP2) 反应。有趣的是，ROS 对核形状和大小（表明表型变化）的影响是由 I 型胶原蛋白基质的硬度控制的，这表明根据 ECM 条件，对微环境化学暴露的表型反应存在阈值。
Oxidative stress-mediated cancer progression depends on exposure to reactive oxygen species (ROS) in the extracellular matrix (ECM). To study the impact of ROS levels on preinvasive breast cancer cells as a function of ECM characteristics, we created a gradient-on-a-chip in which H2O2 progressively mixes with the cell culture medium within connected microchannels and diffuses upward into the ECM of the open cell culture window. The device utilizes a paper based microfluidic bifurcating mixer insert to prevent leakage and favor an even fluid distribution. The gradient was confirmed by measuring H2O2 catalyzed into oxygen, and increasing oxidative DNA damage and protective (AOP2) response were recorded in 2D and ECM-based 3D cell cultures. Interestingly, the impact of ROS on nuclear shape and size (annunciating phenotypical changes) was governed by the stiffness of the collagen I matrix, suggesting the existence of thresholds for the phenotypic response to microenvironmental chemical exposure depending on ECM conditions.