A New Method for the Study of Cell Detachment

Tumor cells that detach and enter the bloodstream create the possibility for the disease to spread in other tissues. While scientists gained knowledge about how cancer cells attach to these surfaces, little is known about the way these cells detach from the initial tumor and a better understanding of this starting point for metastasis could lead to improvements in cancer therapies.

These were the premises from which scientists at Johns Hopkins’ Whiting School of Engineering started the development of an innovative method for studying this phenomenon, creating a lab-on-a-chip device that can help researchers study cell detachment.

The device consists of an array of gold lines, on which molecules promoting the formation of cell attachments are tethered to like balloons tied to string, positioned on a glass slide; a cell placed on the chip will then spread across several of the gold lines, forming attachments to the surface of the chip with help from the molecules which are later released from one of the gold lines trough electrochemical reduction. The portion of the cell corresponding to the detached molecules loses its grip on the surface of the chip, pauses for a moment and then contracts forcefully toward its other end, which is still attached to the chip.
“It’s very dramatic. The cell stretches way, way out across the chip and then, on command, the tail snaps toward the body of the cell” says Denis Wirtz, a Johns Hopkins professor of chemical and biomolecular engineering and co-author of the Nature Methods paper about this phenomenon, which scientists were able to film under a microscope.

After several live-cell experiments performed under different conditions using the chip were recorded, researchers are confident that they are at the beginning of understanding the processes that regulate cell detachment at the molecular level.

Image:
Johns Hopkins Cell Detachment Research with Lab-on-a-Chip At left, the illustration shows adhesive complex formed between cell membrane-bound protein (integrin in gray) with peptide (RGD in red) tethered by thiol molecules (blue) to gold electrode (yellow) on glass slide (green). At right, electrochemical release of tethered peptide from the gold electrode results in local release of the RGD-integrin complex. (Credit: Diagram by Peter Searson)