LeDuc studies significance of mechanics in cell signaling

As the world becomes more connected through advancements in technology and communication, interdisciplinary and collaborative studies become increasingly significant in the scientific community. Philip LeDuc, a professor of mechanical engineering at Carnegie Mellon studying the mechanical aspects of cellular communication, is one of many researchers involved in this type of collaborative research.

LeDuc led a research team along with Lance Davidson, an associate professor of bioengineering at the University of Pittsburgh, and William C. Messner, department chair and professor of mechanical engineering at Tufts University School of Engineering, which used a microfluidic control system to understand how mechanics play a role in how cells communicate.

“It’s a fantastic collaboration between Davidson, a developmental biologist, Messner, who is interested in control theory from a mechanical perspective, and me, who is interested in cell mechanics and applying microtechnologies to biology,” LeDuc explained. “The three of us are all corresponding authors, so it was a great instance of what happens when you bring people from different thought patterns together.”

The research team aimed to stimulate the local region of a tissue, and observe how this signal was propagated throughout the rest of the tissue, in order to determine the significance of mechanics in cell signaling. The use of non-bioengineered tissue allowed the model to be truly a physiological representation, but created obstacles regarding local stimulation. “We took tissue that was already physiological and observed how it works together, but local stimulation is hard to do in biology,” LeDuc said. “If you have a piece of tissue, and pipette in a chemical on top of it, the chemical diffuses within seconds over the entire tissue, so you can’t have local stimulation for long periods of time.”

In order to overcome this obstacle, the team used a microfluidics based system composed of two streams. Each stream was in laminar flow, meaning the streams flowed in parallel layers without lateral mixing. By flowing a chemical over one side of the tissue, the researchers were able to locally stimulate the tissue. “We flowed a chemical over local regions of the tissue which caused a mechanical contraction inside of the system,” LeDuc explained. “We then watched the way the entire 3-D population responded.”
With the ability to locally stimulate a tissue, the researchers were able to test chemical versus mechanical signaling in order to understand the mechanisms involved in cell signal propagation.

“Most people assume cell signaling is immediately chemical,” LeDuc said. “In most cases this is true, but in this case we’re looking at contractility which is a mechanical sense.” The researchers used a chemical called heptanol to determine how much of cell signaling is chemical and how much is mechanical. “Heptanol shuts down the cell’s ability to chemically send signals back and forth by inhibiting their cell junctions,” explained LeDuc.

The researchers found that when chemical signaling was inhibited, propagation was decreased twofold, versus a fourfold decrease in propagation when mechanical signaling was inhibited. This implies that mechanical signaling functions as an important part of cell signaling. “Mechanical signaling is actually twice as important as chemical signaling in this particular context, which runs against the current paradigm; people usually say it’s all chemical,” LeDuc said. “Chemistry still dominates, but mechanics affects chemistry.” LeDuc noted that this research could have various applications in the future. “We are not specifically focused on tackling a disease, but these results could lead to advances in various areas,” LeDuc said.

Cell communication plays an integral part in tissue development. This understanding of cell signaling could lead to advancements in the understanding and treatment of aging and birth defects, both areas that involve the growth and proliferation of cells.

One can also draw a parallel to cancer research. Embryonic development involves rapid growth, while cancer involves a loss of control of rapid growth. Understanding the mechanisms behind cell communication and how this affects the rapid growth could potentially lead to advancements in cancer research and treatment.

The research was published in the Sept. 23 issue of the Proceedings of the National Academy of Sciences.