Diagrams of chemical signaling networks look as intricate as any Rube Goldberg contraption, and chemical equilibria in cell biology are often called switches. Metaphors aside, biological molecules do actually have their mechanical aspects. For example, molecules may snap together to form complexes that act like zippers, gates, or pumps.
Mechanics is also at work at a slightly larger scale—the pushes and pulls cells exert on each other when they contract or relax. These movements, it turns out, are essential to cell-to-cell signaling. According to scientists from Carnegie Mellon University and the University of Pittsburgh, contractility responses sometimes depend more strongly on intercellular mechanical connections than on chemical cues.
A study led by Carnegie Mellon’s Philip LeDuc and Pitt’s Lance Davidson explored how cell contractility is triggered within an embryonic epithelial sheet by local ligand stimulation and coordinates a long-range contraction response. They published their results September 22 in the Proceedings of the National Academy of Sciences, in an article entitled, “Mechanochemical actuators of embryonic epithelial contractility.”
“Our custom microfluidic control system allows spatiotemporally controlled stimulation with extracellular ATP, which results in locally distinct contractility followed by mechanical strain pattern formation,” wrote the authors. “The stimulation–response circuit exposed here provides a better understanding of how morphogenetic processes integrate responses to stimulation and how intercellular responses are transmitted across multiple cells.”
Essentially, the researchers used a microfluidics device that enabled them to “touch” as few as three or four cells. By exercising such fine control over tiny parts of a multicellular tissue, the researchers were able to disable the mechanical connections between the cells without obliterating the delicate underlying processes. These processes, which depended on proteins moving within cells, were visualized with a high-resolution laser scanning microscope.
Disengaging the mechanical connections, the researchers found, substantially reduced the ability of cells to communicate with each other. Although the cells communicated through chemical signaling as well, the cells’ mechanical connections—their ability to push and pull on each other—were dominant in transmitting the signals.
“It’s like 19th century scientists discovering that electricity and magnetism were the same force,” said Davidson. “The key here is using mechanical engineering tools and frameworks to reverse-engineer how these biological systems work, thereby giving us a better chance to develop methods that affect this cellular communication process and potentially treat various diseases related to tissue growth.”
“We proved that mechanical processes are absolutely important along with chemical,” LeDuc added.
The investigators concluded that their findings could provide a better understanding of contractility-dependent morphogenetic movements as well as the intercellular communication pathways critical during developmental biology, synthetic morphogenesis, and multicellular mechanotransduction signaling. They even speculated that their work could lead to a biological actuator that could actively drive morphogenesis.
“If you are dealing with someone who has a birth defect, and their heart didn't form correctly, the question is how do you target it?” LeDuc asked. “This discovery leads us to believe there is a mechanical way to influence tissue development and one day help the cells better communicate with each other to heal the body.”