Hybrid microfluidics platform for studying electrotaxis of glioblastoma

Aberrations in astrocytes are among the most pressing concerns in brain tumor research, especially with regarding the aggressive glioblastoma. Local electric fields generated by nearby neurons have shown to play a role in the movement of such cancer cells, but recreating the microenvironments of brain tumors in the laboratory remains difficult.

Tsai et al. demonstrated a hybrid microfluidic platform for studying glioblastoma electrotaxis. By combining the microfluidic system with a high-throughput machine learning approach for single cell tracking, the group observed how voltage-gated ion channels influence cell movements in two different models of glioblastoma, and charted the effects of the ion channels on cancer cell migration.

The platform works by equalizing the hydrostatic pressure difference between the microchannel’s inlets and outlets, allowing uniform single cells to be seeded reliably.

“The microfluidic platform and the AI image analysis software we have developed drastically increase the experimental throughput and accuracy for similar single cell migration studies,” said author Paul Hsieh-Fu Tsai. “Furthermore, we have found that different voltage-gated ion channels affect the migration of different brain cancer cells.”

They found that electrotaxis of the U-251MG glioblastoma model depends on P/Q-type voltage-gated calcium channels, whereas that of the T98G model depends on R-type channels. Both models rely on rapidly inactivating A-type potassium channels.

Looking forward, Tsai hopes to investigate how the astrocytes interact with other components of the brain’s architecture, such as blood vessels, with the ultimate goal of finding ways to disrupt their electrotaxis and make headway on treating the deadly disease.

Source: “Voltage-gated ion channels mediate the electrotaxis of glioblastoma cells in a hybrid PMMA/PDMS microdevice,” by Hsieh-Fu Tsai, Camilo IJspeert, and Amy Q. Shen, APL Bioengineering (2020). The article can be accessed at https://doi.org/10.1063/5.0004893 .