November 20, 2006
Watching a Tumor Cell Migrate
Using a microfluidics device designed to reproduce the physical microenvironment of small blood vessels and the spaces between cells, researchers at the National University of Singapore have imaged single tumor cells deforming as they migrate through the device. This tool could prove useful for studies aimed at better understanding metastasis and in high-throughput drug assays designed to identify molecules that alter cell migration.
Reporting its work in the journal Microvascular Research, a research team led by M. Mani Maran, Ph.D., described the construction of their cell-movement monitoring device using standard lithographic techniques. The main feature of the device is a set of three parallel microfluidic channels, each separated from the other by a perpendicular row of gaps of either 3 micrometers or 10 micrometers in width. A single cell travels through either of the outer two channels, while a solution containing a chemoattractant – a chemical that triggers cells migration – flows through the center channel. The entire device sits on a microscope to enable real-time imaging of cell movement through the device.
The researchers studied cell migration using three different human tumor cell lines, all of which behaved similarly in the device. Cells flowing through the channel lined by 10 micrometer gaps moved readily through the gaps into the center channel, and the researchers were able to measure the velocity with which the cells moved and observe how the cells deformed as they slid through the channels. In contrast, cells flowing through the channel lined by 3 micrometer gaps probed the gaps but did not cross into the center channel. The investigators observed the cells stopping a gap, probing it, and then backing off and continuing down the channel to the next gap. The researchers were able to monitor cells in the device for up to five days before the cells died.
By forcing the cells to pass through the 3 micrometer gaps – the researchers did not detail how they accomplished this feat – the investigators were able to compare how the cells deform as they pass through the larger and smaller spaces. From these data, the researchers concluded that the membranes of the cancer cells cannot withstand the two-fold increase in surface tension that occurs when crossing through the smaller gap compared to the larger gap. They note that these findings suggest that it may be possible to target cell membrane elasticity as a means of killing metastatic cancer cells.
This work is detailed in a paper titled, “A quantitative observation and imaging of single tumor cell migration and deformation using a multi-gap microfluidic device representing the blood vessel.” Investigators from the National University of Singapore also participated in this study. An abstract of this paper is available through PubMed.