Researchers direct cellular reactions with light

Hopkins researchers have refined a technique for manipulating individual molecules within living cells, allowing them to control where they are moved to at a specific time.

Their findings, published last Dec., give scientists greater control than ever before over moving around molecules and thus influencing cell behavior and growth.

The movement and communication of a single molecule within a cell can help scientists investigate how the cell changes shape, divides or grows. The technique involves using light to specify where proteins should be delivered within a cell.

“This is somewhat similar to GPS coordinates,” said Takanari Inoue, assistant professor of cell biology and member of the Center for Cell Dynamics in the Institute for Basic Biomedical Sciences. Delivering these specific proteins enables the control of cell behavior.

Also involved in the experiment were Tasuku Ueno and Christopher Pohlmeyer of Hopkins, and Tetsuo Nagano and Nobuhiro Umeda of The University of Tokyo.

“The field of cell biology has seen remarkable progress in the last 10 years due to the emergence of fluorescence imaging,” Inoue said.

Fluorescence imaging has shown the importance of the organization of molecules for cell mechanisms. Until now, however, experimental tools have been limited because it was difficult to perturb cells in such a small space in a limited amount of time.

These challenges had been acknowledged by Inoue and his fellow researchers prior to the experiment.

“Many molecules move very rapidly inside and outside cells due to what is known as molecular diffusion,” Inoue said. “So it was a pleasant surprise to see that the experiment worked out nicely.”

Their success can be at least partially attributed to their use of light, which is easy to control and allows for the manipulation of very small regions within cells. Specifically, the researchers attached a light-triggered chemical to a molecule.

Shining an ultraviolet light onto the molecule caused the bond to break, allowing the chemical to force two specific proteins to act where they normally wouldn’t. The researchers took advantage of this unusual interaction by using it to transport proteins to specific locations.

The proteins to be mingled were then attached to special molecules, one of which sent the proteins to the edge of the cell and another of which sent ripples from the edge of the cell. The function of the latter was so that the experimenters would know if and when the proteins were interacting.

Next, the modified proteins were placed inside human skin cells and treated with the light-triggered chemical. After shining a UV beam on 10 percent of the edge of the cell, the researchers found that the ripples only appeared around where the light was directed, suggesting that the chemical tool could be used to move cells to a precise location.

In fact, Inoue suggests that in larger cells, this tool could be used to monitor as little as one percent of the cell.

This study speaks to a question that has preoccupied scientists in the cell migration field for a long time: how cells, even when in a uniform environment, tend to break symmetry.

According to Inoue, their results will help us understand the significant roles cell migration plays in diverse situations, including immune response, wound healing and organ development.