Piezo proteins, sculptors in organ growth
Butterfly wings, fish fins and human limbs develop precisely and symmetrically. While genetics and chemical environment significantly influence their development, recent research has revealed that mechanical forces play a pivotal role as well.
Piezo proteins have the unique ability to convert mechanical forces — such as the pressure and stretch of developing cells — into chemical signals. While these proteins have been previously shown to regulate blood pressure and sense pain, chemical and biomolecular engineers at the University of Notre Dame have demonstrated their crucial role in organ growth, regulating organ size and the arrangement of cells in organ tissue.
Their results were published in Cell Reports.
“Piezo acts like the thermostat in your house. It’s constantly measuring and adjusting the conditions of the cells,” said Jeremiah Zartman, associate professor of chemical and biomolecular engineering at the University of Notre Dame.
Fruit flies, with their fully sequenced genome, provided Zartman’s lab with a well-studied model for organ development that has many commonalities with organ growth in humans.
While it was known that Piezo proteins play a multifaceted role in cell growth and differentiation, the researchers were after a holistic picture of how this protein functioned on the larger scale of organ development.
On a cellular level, Piezo proteins join to create a gated channel into the cell membrane. Under mechanical tension, the channel’s gate opens, allowing calcium ions to flow in. The concentration of these ions cues the cell’s next step — proliferate, push other cells out or undergo programmed cell death.
The team reverse engineered this signaling process, altering the levels of Piezo with drugs or genetic manipulations to better understand how these channels function. The resulting wing asymmetries, aberrant cell death and changes in cellular proliferation highlighted the protein’s fundamental importance in organ development, even to nonadjacent tissues.
“It was a major surprise to us to find a protein, one that exists predominantly in the cell membrane, that could specifically control robustness or precision,” said Zartman. “Piezo regulates how cells interact with each other, reach a certain size, and stop growing. And it does this to ensure significant precision. There’s very little difference between one side of an organ and the other.”
Moving forward, Zartman said that his multi-institutional team will use mice and fish to explore how Piezo signals healthy cell development versus cancerous growth.
The team’s ongoing work is funded by the National Science Foundation’s Emergent Mechanisms in Biology of Robustness, Integration & Organization (EMBRIO) Institute and was supported by the National Institutes of Health’s National Institute of General Medical Science (NIGMS) with early support from the NSF-Simons Center for Quantitative Biology Pilot program.
Contact: Brandi Wampler, associate director of media relations, 574-631-2632, brandiwampler@nd.edu
Latest ND NewsWire
- Danielle Allen discusses the current state of democracy, encourages focus on state governmentSpeaking as part of the 2024-25 Notre Dame Forum, Danielle Allen, the James Bryant Conant University Professor and director of the Allen Lab for Democracy at…
- In memoriam: Elizabeth Nanovic, founding benefactor of the Nanovic InstituteElizabeth Nanovic, a founding benefactor and advisory board member of the Nanovic Institute for European Studies, part of the Keough School of Global Affairs at the University of Notre Dame, passed away on March 30. She was 90.
- Meruelo Center partners with Visa to launch inaugural Visa Fintech Foundations programThrough a pilot partnership between Visa and the Meruelo Family Center for Career Development, University of Notre Dame undergraduate students now have the opportunity to learn about the financial technology (fintech) industry while also exploring career possibilities in the field.
- ‘Quiet eye’: Notre Dame psychologist identifies links between a steady gaze and elite performanceIn a recent study supported by the U.S. Naval Research Laboratory and the Army Research Institute, Notre Dame psychologist Matthew Robison documented a phenomenon in eye movement — or “oculomotor dynamics” — that links a steady, focused gaze with superior levels of performance.
- New On Purpose immersion experiences help Notre Dame students hone their moral compasses over spring breakThis year, the Institute for Ethics and the Common Good (ECG) launched On Purpose, a new education and formation opportunity. Inspired by the 2024–25 Notre Dame Forum theme of “What do we owe each other?”, the On Purpose program creates immersion experiences that allow undergraduates to engage with practitioners who demonstrate profound commitments to human dignity in challenging situations.
- ‘Who the messenger is matters’: Cultural leaders can positively influence population growthFertility rates across the world have been steadily dropping since 1950. Pinpointing the reasons is at the heart of Lakshmi Iyer's work as a professor of economics and global affairs. Her research exemplifies the kind of population-level research that Notre Dame Population Analytics (ND Pop), a new research initiative at the University, seeks to foster.
