Biologists have known for centuries that cells change shape to move, divide, and interact with other cells. But it has been harder to figure out exactly “how” cells do this. For the first time, a team of biophysicists, chemists at the University of Maryland and the biologists at National Institutes of Health has determined why thetexture of external surfaces plays a huge role in cells’ ability to react to their environment. It was my great pleasure and a huge opportunity to be an important part of this fantastic research team. Much like a car requires pavement with just the right level of roughness, cells propel themselves forward more efficiently over surfaces covered in nanoscale patterns. Scientists developed new nanoscale-patterned surfaces that can guide cells to move in specific directions, over nearly limitless distances. The textured surfaces are covered with either parallel ridges or tiny sawtooth-shaped features oriented in the same direction. Imagine, similar surfaces could one day help in the development of new nanotechnology applications, such as highly effective wound dressings and stents that can accelerate the healing process. We studied movement in the single-celled amoeba Dictyostelium discoideum, as well as in human white blood cells. One of the biggest achievement was that we were able to guide the collective migration of highly metastatic breast cancer cells in a single oriented direction. The fact that this mode of guidance works in both primitive and highly evolved cells suggests that cell guidance is important across all living things. To understand the underlying mechanism, we focused our attention to the cytoskeletal protein “actin”, which forms chains that make up a cell’s flexible internal skeleton. One of our important findings show that the sawtooth patterns described above, can guide the disassembly and reassembly of these actin chains, which in turn can propel the cell in a preferred direction of motion.
Imagine a cell as a mosh pit that has a large rubber band surrounding the group of dancers. The dancers represent the actin proteins and the rubber band represents the cell membrane. The dancers in the pit shove against each other, which in turn pushes against the rubber band, changing the shape of the mosh pit. Cells use their actin chains to move away from toxic chemicals, or toward nutrients and other beneficial signals. The chemical signals that normally cause cells to move are only effective if they are close enough and strong enough for the cell to react. To continue the mosh pit analogy, these chemical signals will attract the cell in the same way that loudspeakers attract a mosh pit full of dancers. This scenario is similar to the chemical signaling that directs motion in biological systems. This is a powerful mechanism, but it can only work over a limited distance. The new sawtooth surfaces provide a foothold for the cell’s internal skeleton, allowing the cell to move in one direction, over distances limited only by the size of the sawtooth surface. Imagine that the dance floor is composed of rows of sawteeth about the size of someone’s foot. It is easy to move up the gently sloped side of the sawtooth, but it is hard to move in the other direction against the vertical edge of the sawtooth. As soon as someone starts moving along a row of sawteeth, the people nearby will start to do the same. In this manner, features on the floor that are much smaller than the mosh pit can still cause the group of dancers to move in a preferred direction. Each sawtooth is much smaller than the cell, so as soon as a cell clears one sawtooth, the cell’s actin fibers will already be engaged with the next several sawteeth down the line. This allows the cell to cover nearly limitless distances, so long as it has uninterrupted access to the sawtooth surface.
This discovery shows that we can design patterned surfaces that can control cell behavior through manipulation of actin chains. This capability opens the door to measuring and engineering cell behaviors through similar patterned surfaces, which will have many potential biomedical applications
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About the author: Satarupa Das is a Scientist at the Institute of Physical Sciences & Technology (Maryland, USA) and in this blog she writes about her recent publication titled “Asymmetric nanotopography biases cytoskeletal dynamics and promotes unidirectional cell guidance (PNAS, 2015; http://www.pnas.org/content/112/41/12557.long)
About the image: Unidirectional guided movement of an active human white blood cell (Tagged with Lifeact-GFP; source- Satarupa Das)
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