The effect of glucose restriction on cancer cell contractility: A threshold response in U-87 glioma

Abstract

Cells rely on contractility to proliferate, and cancerous ones exhibit an increased glucose dependence. It is therefore hypothesized that glucose restriction can mitigate cancer cell proliferation by stunting their contractility. However, glucose-restriction studies have mostly been based on experiments that have yielded conflicting results; some cells become less contractile under glucose-restriction, intuitively, while, others become surprisingly more contractile. Active mechanistic modeling may prove fruitful in resolving these conflicts. In this study, we develop a model for glucose-mediated cell contractility to capture the mechanical implications of glucose restriction. The model is calibrated on cell contraction data taken from 2D-cultured glioma cells, laying on a collagen substrate. The model predicts the existence of a critical level of glucose restriction that must be exceeded for contractility to be affected, and this is validated by our experiments. Our model provides an initial step toward a fundamental understanding of the metabolic implications of cell contractility, particularly in the context of glucose restriction: an essential step in cancer studies. significanceThis study advances our understanding of how glucose restriction affects cancer cell contractility, an essential factor in cell proliferation. Our findings reveal that cells require severe glucose deprivation before exhibiting reduced contractility, highlighting a threshold response. This indicates that the cytoskeleton, a key structural component, remains active until a significant reduction in energy supply forces the cell into a lower energy state. These insights provide critical knowledge about the metabolic hierarchy within cells, contributing to the broader study of cancer metabolism and potential therapeutic strategies aimed at disrupting cellular energy pathways.