Details

Autor(en) / Beteiligte

• Zanotelli, Matthew R
• Goldblatt, Zachary E
• Miller, Joseph P
• Bordeleau, Francois
• Li, Jiahe
• VanderBurgh, Jacob A
• Lampi, Marsha C
• King, Michael R
• Reinhart-King, Cynthia A
• Garcia, Andres J.

Titel

Regulation of ATP utilization during metastatic cell migration by collagen architecture

Ist Teil von

• Molecular biology of the cell, 2018-01, Vol.29 (1), p.1-9

Ort / Verlag

United States: The American Society for Cell Biology

Erscheinungsjahr

2018

Link zum Volltext

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• Cell migration in a three-dimensional 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 three-dimensional 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 that 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.