A constriction channel analysis of astrocytoma stiffness and disease progression.

Abstract

Studies have demonstrated that cancer cells tend to have reduced stiffness (Young's modulus) compared to their healthy counterparts. The mechanical properties of primary brain cancer cells, however, have remained largely unstudied. To investigate whether the stiffness of primary brain cancer cells decreases as malignancy increases, we used a microfluidic constriction channel device to deform healthy astrocytes and astrocytoma cells of grade II, III, and IV and measured the entry time, transit time, and elongation. Calculating cell stiffness directly from the experimental measurements is not possible. To overcome this challenge, finite element simulations of the cell entry into the constriction channel were used to train a neural network to calculate the stiffness of the analyzed cells based on their experimentally measured diameter, entry time, and elongation in the channel. Our study provides the first calculation of stiffness for grades II and III astrocytoma and is the first to apply a neural network analysis to determine cell mechanical properties from a constriction channel device. Our results suggest that the stiffness of astrocytoma cells is not well-correlated with the cell grade. Furthermore, while other non-central-nervous-system cell types typically show reduced stiffness of malignant cells, we found that most astrocytoma cell lines had increased stiffness compared to healthy astrocytes, with lower-grade astrocytoma having higher stiffness values than grade IV glioblastoma. Differences in nucleus-to-cytoplasm ratio only partly explain differences in stiffness values. Although our study does have limitations, our results do not show a strong correlation of stiffness with cell grade, suggesting that other factors may play important roles in determining the invasive capability of astrocytoma. Future studies are warranted to further elucidate the mechanical properties of astrocytoma across various pathological grades.