A Cell Culture Chip with Transparent, Micropillar-Decorated Bottom for Live Cell Imaging and Screening of Breast Cancer Cells

Abstract

In the recent years, microfabrication technologies have been widely used in cell biology, tissue engineering, and regenerative medicine studies. Today, the implementation of microfabricated devices in cancer research is frequent and advantageous because it enables the study of cancer cells in controlled microenvironments provided by the microchips. Breast cancer is one of the most common cancers in women, and the way breast cancer cells interact with their physical microenvironment is still under investigation. In this study, we developed a transparent cell culture chip (Ch-Pattern) with a micropillar-decorated bottom that makes live imaging and monitoring of the metabolic, proliferative, apoptotic, and morphological behavior of breast cancer cells possible. The reason for the use of micropatterned surfaces is because cancer cells deform and lose their shape and acto-myosin integrity on micropatterned substrates, and this allows the quantification of the changes in morphology and through that identification of the cancerous cells. In the last decade, cancer cells were studied on micropatterned substrates of varying sizes and with a variety of biomaterials. These studies were conducted using conventional cell culture plates carrying patterned films. In the present study, cell culture protocols were conducted in the clear-bottom micropatterned chip. This approach adds significantly to the current knowledge and applications by enabling low-volume and high-throughput processing of the cell behavior, especially the cell–micropattern interactions. In this study, two different breast cancer cell lines, MDA-MB-231 and MCF-7, were used. MDA-MB-231 cells are invasive and metastatic, while MCF-7 cells are not metastatic. The nuclei of these two cell types deformed to distinctly different levels on the micropatterns, had different metabolic and proliferation rates, and their cell cycles were affected. The Ch-Pattern chips developed in this study proved to have significant advantages when used in the biological analysis of live cells and highly beneficial in the study of screening breast cancer cell–substrate interactions in vitro.

Epithelial-Mesenchymal Transition of Cancer Cells on Micropillar Arrays

“…59−61 Cell nuclei undergo severe deformation on micropillar arrays with an appropriate dimension, which influenced cell behaviors. 62 Nuclear deformation can also cause chromatin condensation and chromosome relocalization within the nucleus and alter gene expression of the cells. 63−66 It has been demonstrated that actomyosin and microtubule may synergistically regulate nuclear deformation and chromatin remodeling, finally modulating gene expression.…”

“…The interaction between cells and materials is a fundamental issue in the fields of biomaterials and tissue regeneration. − Micropillar arrays provide a unique kind of topological surfaces to regulate cell-material interactions. − Cell nuclei undergo severe deformation on micropillar arrays with an appropriate dimension, which influenced cell behaviors . Nuclear deformation can also cause chromatin condensation and chromosome relocalization within the nucleus and alter gene expression of the cells. − It has been demonstrated that actomyosin and microtubule may synergistically regulate nuclear deformation and chromatin remodeling, finally modulating gene expression .…”

Water-Soluble Biomass Resist Materials Based on Polyglucuronic Acid for Eco-Friendly Photolithography

“…Nanotechnology, operating at an atomic and molecular scale, represents the fourth industrial revolution, profoundly influencing contemporary society [1]. In the realm of nanotechnology, microfabrication plays a pivotal role not only in manufacturing integrated circuits for the semiconductor industry but also in various domains, such as electronics, micro electromechanical systems (MEMS) devices, microfluidics, cell culture, and regenerative medicine in tissue engineering [2][3][4]. Focusing on applications in the biological domain, micro-and nanofabrication techniques hold immense potential for tailoring biomaterials with desired characteristics [5,6].…”