Journal
ACS BIOMATERIALS SCIENCE & ENGINEERING
Volume 4, Issue 2, Pages 432-445Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsbiomaterials.7b00087
Keywords
3D cell culture; oxidative stress; cancer progression; DNA damage; nuclear morphology; cell nucleus
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Funding
- Office of Vice President for Research and Partnership
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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.
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