Sooraj Shah ’24

With more than 1.9 million individuals in the US being diagnosed with cancer each year, research revolving around the behavior of cancer cells is an important aspect of the search for better treatments. The study of cancer cells in biological assays within a lab has led to great research regarding the structure, motion, and activity of cancer cells in-vitro. A specific part of lab work is the viscosity at which cells are cultured in, which hovers around 0.77 centipoise (cP), but no more. A study led by Dr. Kaustav Bera, a professor in the department of chemical and biomedical engineering at Johns Hopkins University, focused on how a higher viscosity may affect the response of cancer cells to observe the mechanisms by which cancer cells can sense viscosity.
To test this theory, the researchers achieved different viscosities by dissolving macromolecules into the cell-culture media. Cells were then tracked using live-cell imaging software, from the initial 3D spherical structure. Cell movement was also monitored in two dimensions, and cell-signaling pathways of the cancer cells in response to increasing viscosity were tracked using microscopy and electrophysiological detection based methods.
The results showed cells surrounded by a higher viscosity exhibit higher and faster movement than inert particles. A major reason for this comes from the high mechanical force exerted on the cell, which in turn makes the protein called actin within the cell membrane to become more dense. In addition, a membrane protein called NHE1 facilitates the transport of protons into the cytosol, allowing for the intake of water via an aquaporin protein. This increased water intake allows increased movement through small spaces. Lastly, calcium intake is also increased, which allows greater contraction of the cell, thus working with the increased actin density to move through higher viscosities quicker.
While this discovery of cell movement is intriguing, the next goal would be using this research to find how to control the movement of these cancer cells. Limiting the movement of cancer cells in increasingly viscous environments may provide a way to target them at one time during treatment. Bera plans to use this research to fuel other avenues, testing how viscosity of extracellular fluid may affect other biological functions.
Works Cited:
[1] Bera, Kaustav, et al. “Extracellular Fluid Viscosity Enhances Cell Migration and Cancer Dissemination.” Nature, vol. 611, no. 7935, 2022, pp. 365–373., https://doi.org/10.1038/s41586-022-05394-6.
[2] Image Retrieved from: https://images.unsplash.com/photo-1576086213369-97a306d36557?ixlib=rb-4.0.3&ixid=MnwxMjA3fDB8MHxzZWFyY2h8Mnx8Y2FuY2VyJTIwY2VsbHN8ZW58MHx8MHx8&auto=format&fit=crop&w=400&q=60