New Cancer Factor: How a “Viscous” Environment Influences Brain Tumor Cells

A new study published in the journal Microsystems & Nanoengineering suggests that the behavior of glioblastoma cells — one of the most aggressive forms of brain cancer — is influenced not only by the chemical environment and tissue stiffness, but also by the viscosity of the surrounding fluid.

The work was carried out by researchers from the Chongqing Central Hospital and Chongqing University. The scientists developed a new experimental platform — a two-layer open microfluidic chip — that allows long-term observation of cells under controlled viscosity conditions. This is important because traditional closed systems poorly replicate real tumor conditions: they restrict access to oxygen and nutrients and distort the mechanical forces acting on cells.

The experiment involved two human glioblastoma cell lines (U-251 and LN-229), which were cultured for a month in a high-viscosity environment resembling the invasive periphery of a tumor.

Although a more viscous environment would normally be expected to slow movement, the cells adapted to these conditions actually migrated faster and farther than the control cells. At the same time, they became smaller and more flexible, allowing them to pass more easily through narrow spaces within the device’s microstructure.

At the cellular level, researchers observed significant mechanical compression of the nuclei and activation of the YAP protein, which plays a role in mechanosensitive signaling pathways. In one of the cell lines (U-251), this was accompanied by stable changes in the expression of genes associated with tumor invasiveness, including CD44, FN1, and MMP9. In the second cell line (LN-229), changes in shape and mobility were similar, but long-term genetic reprogramming was minimal.

Notably, some molecular changes persisted even after the cells were returned to a normal-viscosity environment. This suggests that tumor cells may develop a form of mechanical “memory” that continues to influence their behavior over time.

The authors emphasize that the new open microfluidic system makes it possible to separate the effects of fluid viscosity from the mechanical confinement caused by surrounding walls, factors that are usually combined in conventional models. This makes the platform a more accurate representation of real tumor conditions and opens possibilities for testing drugs that target mechanosensitive pathways, including the YAP signaling protein and the cytoskeleton.

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