Cancer mechanics and elastic gradient substrate

Adele Khavari

A) Schematic of the fabrication set up. To create a stiffness gradient, coverslips covered with photo-sensitive PDMS with a thickness of 200µm were irradiated with UV under variable exposure time by moving the UV mask with a constant speed. B) Local Young’s Modulus (LYM) as a function of the position and speed of mask movement. Increasing mask’s speed from 0.5µm/min to 2µm/min varied gradient steepness from 7kPa/mm to 20kPa/mm. C) Glucose consumption rate /fluorescence decay of glucose as a function of cell contractile work for 67NR (non-metastatic) and 4T1 (metastatic) cells on 3kPa and 50kPa substrates. Each data point is a single cell at least from three separate experiments. and error bars are analysis and experimental errors.

Extracellular matrix (ECM) stiffening and increased cell contractility are associated with cancer progression. While increased metabolic activity is also linked to aggressive cancers, how ECM mechanics and cancer cell metabolism directly relate to cell contractility remains unclear. In our research we have developed an elastic gradient PDMS substrate to measure cellular contractility in response to mechanical challenges, finding that metastatic cancer contractile work increases non-linearly as they are challenged with stiffer microenvironments. We’ve found that metastatic cancer cells sustain their contractility upon glucose and L-glutamine starvation, yet when provided with glucose following starvation, they consume it almost three times faster than non-metastatic cancer cells. We also see that the glucose consumption rate linearly increases with cell contractile work. These results suggest that the metabolic adaptability of highly metastatic cancer cells enables increased contractile work to overcome environmental mechanical changes during cell migration.

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Department of Bioengineering

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