Molecular Biology of the Cell
Molecular Biology of the Cell
5 years ago

Regulation of ATP utilization during metastatic cell migration by collagen architecture.

Matthew R Zanotelli, Michael R King, Jiahe Li, Marsha C Lampi, Francois Bordeleau, Joseph P Miller, Zachary E Goldblatt, Cynthia A Reinhart-King, Jacob A VanderBurgh
Cell migration in a 3D matrix requires that cells either remodel the surrounding matrix fibers and/or squeeze between the fibers to move. Matrix degradation, matrix remodeling, and changes in cell shape each require cells to expend energy. While significant research has been performed to understand the cellular and molecular mechanisms guiding metastatic migration, less is known about cellular energy regulation and utilization during 3D cancer cell migration. Here, we introduce the use of the genetically encoded fluorescent biomarkers, PercevalHR and pHRed, to quantitatively assess ATP, ADP, and pH levels in MDA-MB-231 metastatic cancer cells as a function of the local collagen microenvironment. We find that the use of the probe is an effective tool for exploring the thermodynamics of cancer cell migration and invasion. Specifically, we find the ATP:ADP ratio increases in cells in denser matrices, where migration is impaired, and it decreases in cells in aligned collagen matrices, where migration is facilitated. When migration is pharmacologically inhibited, the ATP:ADP ratio decreases. Together, our data indicate that matrix architecture alters cellular energetics, and that intracellular ATP:ADP ratio is related to the ability of cancer cells to effectively migrate.

Publisher URL: http://doi.org/10.1091/mbc.E17-01-0041

DOI: 10.1091/mbc.E17-01-0041

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