Scientists in the US have built a tiny device that can separate some types of cancerous and non-cancerous cells. Resembling a ratchet, the device exploits the fact that different cells use different strategies to squeeze their way through narrow passages. The team believes that similar ratchets could be used to trap “metastatic” cancer cells, which can spread the disease throughout the body.
Metastasis is the process by which cancer cells break away from a tumour and move through the body — creating more tumours and often decreasing a patient’s chance of survival. Understanding how these cells move could lead to new medical treatments that stop metastasis — or even the development of “cancer traps” that remove cancer cells from circulation.
Now the physical chemist Bartosz Grzybowski and his colleagues at Northwestern University in Chicago have shown that it is possible to sort different types of cells according to how the cells move through tiny ratchet-like structures.
The team created the ratchets by etching channels into a flat gold surface. Their first design resembled a series of triangles, each about 50 μm across. One triangle funnels into the next and so on (see Moving along a ratchet).
The team studied the behaviour of three different types of cells — two that are involved in cancer metastasis, and one that is not. In all cases they found that the cells moved through the ratchet in the direction of the funnels but not in the opposite direction.
Anchors away
To understand this unidirectional behaviour, the team studied a series of microscope images that revealed how a cell’s cytoskeleton — internal filaments that define the shape of the cell — changes as it moves along the ratchet. A cell introduced into a triangle first adopts the triangular shape of its surroundings by pushing filaments of the protein actin into the three corners. The cell then “realizes” that it can squeeze through only one corner of the triangle, and does so by stretching an actin protrusion into the next triangle.
The protrusion “anchors” against the back side and corners of the next triangle and pulls the rest of the cell along with it. The process, which can take several hours to complete, then repeats itself. While cells did occasionally send out protrusions in the opposite direction along the ratchet, these found nowhere to anchor.
Although all three types of cell used this technique to move thought the ratchet, the team noticed that the non-cancerous cells tended to send out much longer protrusions than the cancer cells — often extending two triangles forward. With this in mind, the team designed a second ratchet that sends cancer cells in one direction and non-cancerous cells in the other direction.
This second ratchet contains a series of barbs (each about 30 μm long) on alternating sides of a channel (see Grabbing hold of a barb). The broad and relatively short protrusions of the cancer cells cannot “grab and pull” as they did in the triangular ratchet. Instead, the cells simply squeeze through the ratchet in one direction. The longer and thinner protrusions of the non-cancerous cells extend further along the ratchet — allowing them to anchor onto a barb and pull these cells in the opposite direction.
Permanent traps
We could have a very new and very powerful tool for fighting metastasizing cancer — with a physical principle Bartosz Grzybowski, Northwestern University
The team believes that this effect could be exploited in devices they have dubbed “cancer traps” — concentric arrangements of ratchets that draw cancer cells to a central region where they are trapped permanently. Grzybowski told physicsworld.com that someday such ratchets could be implanted close to tumours to selectively fish out and trap metastatic cells. “We could have a very new and very powerful tool for fighting metastasizing cancer — with a physical principle”, he says.
Jane Hill, who studies the mobility of single-cell organisms at the University of Vermont, welcomed the research. “Cell mobility in confined geometries was not an area most biologists considered important — mostly because in the past our biochemical point of view has not considered the influence of a cell’s physical environment,” she says. Hill also points out the work could provide insight into whether there are geometries in the body that favour the migration of one cell type over another.
The research is reported in Nature Physics
