The vast majority of cancer deaths are due to metastasis, the spread of cancer cells from its primary site to other parts of the body. These metastatic cells tend to move more than their non-metastatic variants but this movement is poorly understood. Scientists are studying cancer cells intently with the hope they can learn to control the movements of the dangerous cells.
Northwestern University researchers now have demonstrated a novel and simple method that can direct and separate cancer cells from normal cells. Based on this method, they have proposed that cancer cells possibly could be sequestered permanently in a sort of “cancer trap” made of implantable and biodegradable materials.
The demonstrated device, which takes advantage of a physical principle called ratcheting, is a very tiny system of channels for cell locomotion. Each channel is less than a tenth of a millimeter wide. The asymmetric obstacles inside these channels direct cell movement along a preferred direction.
Details are published online by the journal Nature Physics.
“We have demonstrated a principle that offers an unconventional way to fight metastasis, a very different approach from other methods, such as chemotherapy,” said Bartosz Grzybowski, the paper’s senior author. “These are fundamental studies so the method needs to be optimized, but the idea has promise for a new approach to cancer therapy.”
Grzybowski is associate professor of chemical and biological engineering in the McCormick School of Engineering and Applied Science and associate professor of chemistry in the Weinberg College of Arts and Sciences.
The researchers first discovered they could design channels of different geometries — some a series of connected triangles — through which cells can move in a single direction. (Live mammalian melanoma, breast cancer and normal cells were studied.)
To create the channels, the researchers patterned cell-adhesive and cell-repellant chemical compounds onto a substrate. The cells stayed out of the repellant areas and localized onto the “ratchet” channels, which then directed the cells’ movements.
Grzybowski and his colleagues took this knowledge one critical step farther: they designed channels that successfully moved the cells of two types — notably, cancerous and non-cancerous — in opposite directions and thus partly sorted them out.
To sort the cells, they took advantage of the cells’ different shapes and mobility characteristics. Migrating cancer cells tend to be more round and broad while normal, epithelial cells are long and thin with long protrusions on the ends. The researchers designed a channel with “spikes” coming out at 45-degree angles from the walls, alternating on opposite sides of the channel. This pattern funnels cancer cells in one direction while at the same time directing the normal cells in the opposite direction, as those cells “grab” the spikes and pull themselves through.
The researchers showed that a device with a number of these channels leading to a central reservoir, like spokes on a wheel, worked just as well separating cancer and non-cancerous cells. A stack of these radially arranged ratchet channels could be used to create a “cancer trap.”
“When implanted next to a tumor the particles would guide cancer cells, but not normal cells, inward to the reservoir, where they would be trapped,” said Grzybowski. “The particles could also be part of the sutures used during surgical procedures.”
The Nature Physics paper is titled “Directing Cell Motions on Micropatterned Ratchets.” In addition to Grzybowski, the paper’s other authors are Goher Mahmud, Christopher J. Campbell, Kyle J. M. Bishop, Yulia A. Komarova, Oleg Chaga, Siowling Soh, Sabil Huda and Kristiana Kandere-Grzybowska.