Microfluidic Device Measures Dynamics and Mechanical Properties of Actively Invading Cells
Researchers at the Cornell University Physical Science-Oncology Center (Cornell PS-OC) have developed a microfluidic system than makes it possible to study the dynamics of cell invasion and the mechanical changes that occur when cells squeeze through spaces smaller than the cell’s nucleus. This work, led by David Erickson and Cynthia Reinhart-King, was published in the journal Lab on a Chip.
The Cornell PS-OC team fabricated a device with rows of microfluidic channels that they call multi-staged serial invasion channels, or MUSIC. Each channel in the MUSIC device contains several constrictions meant to mimic the narrow gaps that metastatic cancer cells must traverse as they leave a tumor and colonize new sites within the body. The constrictions had diameters smaller than the nucleus, the largest and stiffest organelle in a cell. The investigators created these constrictions in two lengths: one shorter and the other longer than a typical metastatic cell.
The researchers measured movement of highly invasive breast cancer cells through the MUSIC device and observed four distinct phases of migration. In the first phase, the cell migrates in the main channel and then slows down as it approaches the constriction. In phase two, the cell starts moving into the barrier, while in phase 3 the cell stops moving forward and either pauses or moves back and forth within the barrier. Finally, in phase 4 the cell exits the barrier and begins moving forward at a constant speed.
In some cases, the researchers noted that cells could generate contractile forces strong enough to squeeze the nucleus and allow the cell to pass through the barrier. In other cases, the cell rolls backwards and forwards in the barrier, before passing through. This appears to allow cells to find a position that is more amenable to deformation. The study also found that treating the cells with taxol, an anti-cancer drug that stabilizes microtubules, dramatically increases the transit time through the barriers. Analysis of the migrating cells also revealed that cells passing through the constrictions sometimes generated long protrusions that could be up to hundreds of micrometers in length. The investigators hypothesize that these extensive protrusions may make it easier for migrating cancer cells to find nutrients and to home toward blood vessels.
This work, which is detailed in a paper titled, “Elucidating mechanical transition effects of invading cancer cells with a subnucleus-scaled microfluidic serial dimensional modulation device,” was supported by the National Cancer Institute's Physical Sciences in Oncology initiative, a program that aims to foster the development of innovative ideas and new fields of study based on knowledge of the biological and physical laws and principles that define both normal and tumor systems. An abstract of this paper is available at the journal's Web site.