Unlocking Cell Migration

When someone is injured or sick, the body springs into action, clotting blood, and fighting infection. These protection mechanisms involve a flurry of activity within the body. Chemical signals are sent through nerves and other cells like a 911 call to warn of a problem. Platelets and white blood cells then act as first responders, migrating to the wound or source of the infection to handle the emergency.

Scientists understand the signaling part of the process but are trying to get a better handle on the cell migration part. So the National Institute of General Medical Studies has funded a 10-year, $80 million effort known as the Cell Migration Consortium (CMC) to study cell movement through a systems biology approach. “In almost any physiological process, cells have to get from one place to another,” says Dr. Jason Haugh, an associate professor in the Department of Chemical and Biomolecular Engineering. Haugh is designing computer models for CMC to determine how cells organize themselves to begin their journeys.

When a cell receives a signal that it’s time to go, it assumes a polarity, Haugh says. One region of the cell takes the lead, and the rest follows behind in an almost inchworm-like motion. In his simulations, Haugh is studying skin cells known as fibroblasts, as well as cells involved in the immune response, all of which play important roles in wound healing. A video of a fibroblast experiment and the corresponding simulation show the cell lighting up with fluorescence as enzymes inside are activated by chemical receptors picking up the warning signals being sent through the body. “Without a signal to direct the cell, it migrates slowly and follows a random path,” he says. “That is an ineffective strategy if the cell is to arrive at a specific location.”

“When a cell receives a signal that it’s time to move, it assumes a polarity. One area takes the lead, and the rest follows behind in an almost inchworm-like motion.”

Haugh is studying pathways in the cell that he thinks are responsible for establishing polarity. But he says more research is needed to learn how a cell establishes its front and back ends. “The right combination of molecular components is needed to form a new leading edge, and these molecules interact dynamically with respect to location and time,” he says. Other members of the CMC research team will build on Haugh’s findings as they study how cells gain traction and momentum in their movement. “All sorts of physical forces are in play, as well as the biochemistry regulating it,” he says. “It’s a complex problem that we’re trying to approach from different angles.”

 

 

Dr. Jason Haugh studies skin and immune system cells to determine how cells get turned in the right direction to fight infection and heal wounds.

Dr. Jason Haugh studies skin and immune system cells to determine how cells get turned in the right direction to fight infection and heal wounds.

Mouse fibroblasts light up with green fluorescence as they respond to the presence of platelet-derived growth factor (red).

Mouse fibroblasts light up with green fluorescence as they respond to the presence of platelet-derived growth factor (red).