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bioRxiv · 10.1101/694638

Unique Cancer Motility Behaviors in Confined Spaces of Microgroove Topography with Acute Wall Angles

Kushiro, K.·Takai, M.·Yaginuma, T.
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Abstract

In recent years, many types of micro-engineered platform have been fabricated to investigate the influences of surrounding microenvironments on cell migration. Previous researches demonstrate that microgroove-based topographies can influence cell motilities of normal and cancerous cells differently. In this paper, the microgroove wall angle is altered from obtuse to acute angles and the resulting differences in the responses of normal and cancer cells are investigated to explore the geometrical characteristics that can efficiently distinguish normal and cancer cells. Interestingly, trends in cell motilities of normal and cancer cells as the wall angles are varied between 60-120{degrees} were different, and in particular, invasive cancer cells exhibit a unique, oscillatory migratory behavior. Results from the immunostaining of cell mechanotransduction components suggest that this difference stems from directional extension and adhesion behaviors of each cell type. In addition, the specific behaviors of invasive cancer cells are found to be dependent on the myosin II activity, and modulating the activity can revert cancerous behaviors to normal ones. These novel findings on the interactions of acute angle walls and cancer cell migration provide a new perspective on cancer metastasis and additional strategies via microstructure geometries for the manipulations of cell behaviors in microscale biodevices.\n\nStatement of SignificanceCancer metastasis is the leading cause of cancer patient deaths, and yet how the microstructures within the body affect this cell migration phenomenon is not well understood. In this paper, microdevices containing microgroove structures of varying geometries, in particular obtuse and acute angles, were utilized to monitor cell motilities of various cancer cells to understand the influences of the geometrical features of microstructures on cancer metastasis. Surprisingly, it was found that the acute angle geometries lowered the persistence of migration for cancer cells, which was a totally different response from non-cancerous cells. These new findings would enable the next-generation biodevices to analyze, separate and capture cancer cells, as well as shed light onto the underlying mechanisms of cancer metastasis.

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Kushiro, K., Takai, M., Yaginuma, T.. 2019-07-05. Unique Cancer Motility Behaviors in Confined Spaces of Microgroove Topography with Acute Wall Angles. https://doi.org/10.1101/694638

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