Have you ever tried to get a group to work together? If so, how many were you trying to reconcile? With that image in your head, imagine trying to do that with hundreds or even thousands of people. Now, make those people cells which can’t speak and who each want to move in a random direction independent of the group, and you’ll begin to see the wonder that is collective cell migration.
This summer, I am working in the Hoffman Lab studying collective cell migration (CCM). CCM is the process by which hundreds (if not thousands!) of cells move together as sheets, groups, or chains in the same direction with the same velocity. However, each cell is independent and can generate propulsive forces without needing outside help. So, how then can so many cells all stay connected and coordinate their movements? Our lab wants to discover the molecular mechanisms that enable this incredible phenomenon.
Specifically, we are interested in how mechanotransduction, or the conversion of mechanical forces into biochemicals signals, mediates this process. Many key proteins have been identified that deform when the proper force is applied, changing their structure and function. These force-dependent conformations can regulate biochemical pathways that influence complex cellular processes, like the cell coordinating its movement with the larger group. These “mechanosensitive” proteins allow the cell to turn local forces into chemical signals that can impact and influence the entire cell!
But one of the big challenges facing this field is identifying which proteins are involved and how this process is regulated. Much of the actual molecular mechanics of it all is still poorly understood. Until we really have a tighter grasp on these mechanisms, we are hindered in our ability to manipulate CCM, both to understand it better and harness it for future applications in cancer biology, wound healing, and regenerative medicine.
This is where I come in! This summer I am using molecular cloning to engineer fusion proteins which will allow us to study the dynamics of some of these mechanosensitive proteins in live cells. You can think of fusion proteins as the Frankenstein’s monsters of the protein world. By cutting and pasting the DNA using traditional molecular cloning techniques, we can take the mechanosensitive proteins we are interested in and attach a fluorescent protein to the end of it. Because this protein is fluorescent (lights up when hit by the right wavelength of light), we can use this “biosensor” to see the protein in live cells! With this, we can better understand its localization and dynamics in the cell and its involvement in CCM. Additionally, by creating biosensors where the mechanosensitive protein has a single amino acid substitution whose effect on the protein is already known, we can further study the function of our protein in CCM by examining the mutant’s effects relative to the normal biosensor.
So, that’s my plan for the summer. Stay tuned to see if I can actually brighten up the world a bit!
Bonus: These fluorescent proteins lets us take really beautiful pictures of cells and cell sheets! Photo courtesy of Hoffman Lab.