How to Signal a Cell to Move Along a Surface
What gets you moving?
And then how do you make your move? In all walks of life, we find organisms moving across various surfaces in different ways for different reasons. A spider may decide to walk up a wall. Its motivation, its stimulation to do this may be fear or something else, but unlike you or I – the spider actually can walk up a wall. It is able to do this, in part, because of hundreds of thousands of tightly packed bundles of hairs called setules.
Alternatively, there is a palm tree, known as the walking palm tree. This exceptional species of flora has a way of sprouting new heavy roots, causing it to lean forward. The old roots in the back are denied nutrients and rot off. The new roots will eventually become the old roots as it makes its way forward. It is responding and moving its way to sunlight.
What if we were dealing with something exceptionally small – like a cell. What would make a cell move – and how might it move along a surface?
This is the essence of a study out of the Freeman Lab with lead author Kyle Riker, which explored programming cells to respond to signals to move in ways we want them to.
Getting a grip
Imagine you visit a fitness center that has a climbing wall. You stand at the bottom of the wall, you look around and realize there are no pegs anywhere to hold and stand on to get up to the top. With nothing to hold on to, all you can do is stand there in place. But then, someone at the fitness center flips a switch and the pegs appear. Now, you can stretch out and reach for the pegs to move along up the surface of the wall towards the top.
In this study, the Freeman Lab focused upon a cell sitting on a surface populated with strands of peptide. A second peptide strand type that has RGDS (a peptide sequence that cells recognize which will instruct them to spread and adhere to a surface) attached at the end is introduced. When the environment is in its “Off” state, these RGDS-carrying peptide strands are not present. However, when in the “On” state, the RGDS-carrying peptides are added to the system and adjoin, like a game of musical chairs, coiling with the anchored peptide strand. At this point, integrins along the cell’s surface become attracted to the signal of the RGDS. Like our trip to the climbing wall, now the cell, which was sitting there in place, has anchors to reach for, grab on to and move along the surface.
From the paper’s Abstract:
The native extracellular matrix communicates and interacts with cells by dynamically displaying signals to control their behavior. Mimicking this dynamic environment in vitro is essential in order to unravel how cell–matrix interactions guide cell fate. Here, we present a synthetic platform for the temporal display of cell-adhesive signals using coiled-coil peptides. By designing an integrin-engaging coiled-coil pair to have a toehold (unpaired domain), we were able to use a peptide strand displacement reaction to remove the cell cue from the surface.
…This dynamic platform will allow us to uncover the molecular code by which cells sense and respond to changes in their environment and will provide insights into ways to program cellular behavior.
The schematic to the left illustrates this behavior. In the OFF state, our cell sits stationary in the center of the surface. It has nothing to grab on to and is unable to interact with the red coils. But in the ON state, we see the introduced green coils with the RGDS (purple) at the end wrap around the red coils. This in turn, provides a signal to the cell’s integrins (pink) to reach out and connect with, allowing the cell to move along the surface.
Motion is only one outcome of providing reversable signals which a cell can respond to. Come back to discover new ways in which the Freeman Lab is working to guide cells to potentially stop diseases in their tracks and promote healthy biological systems
A Programmable Toolkit to Dynamically Signal Cells Using Peptide Strand Displacement
K Riker, ML Daly, M Papanikolas, T Jian, SJ Klawa, JS Sahin, D Liu, A Singh, AG Miller, R Freeman
ACS Applied Materials & Interfaces, 2021