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
- ND Expert Sean Kassen: Statement on first FDA-approved treatment for Niemann-Pick Type C diseaseToday, the FDA announced the first approved treatment for Niemann-Pick Type C (NPC) disease: an oral medication named Miplyffa (arimoclomol). Sean Kassen, director of the Ara Parseghian Medical Research Fund at the University of Notre Dame, said this represents the beginning of a new and hopeful era for NPC families.
- Notre Dame juniors Faiza Filali, Angela Olvera named Obama-Chesky Voyager ScholarsUniversity of Notre Dame juniors Faiza Filali and Angela Olvera have been named to the third cohort of Obama-Chesky Voyager Scholars. They are Notre Dame’s second and third Voyager Scholars after senior Raleigh Kuipers, who recently returned from Latin America as a member of the second cohort.
- Notre Dame theologian to receive 2024 Ratzinger Prize from VaticanCyril O’Regan, the Catherine F. Huisking Professor of Theology at the University of Notre Dame, has been selected to receive the 2024 Ratzinger Prize in Theology, widely regarded as the most prestigious award in the field. Pietro Parolin, the Vatican’s secretary of state, will present the award to O’Regan and to sculptor Etsurō Sotoo during a ceremony at the Apostolic Palace in Vatican City on Nov. 22. Both winners will also have an audience with Pope Francis earlier that day.
- Keough School invites members of the community to join in International Day of Peace eventsThe Keough School of Global Affairs will observe the International Day of Peace with two campus events: a prayer service featuring University President Rev. Robert A. Dowd, C.S.C., on Friday (Sept. 20) and a talk by a Notre Dame graduate who serves in the Sierra Leone government on Tuesday (Sept. 24). Both events are free and open to the public.
- Notre Dame to host conference on St. Thomas Aquinas, commemorating 800th anniversary of his birthTo commemorate the 800th anniversary of his birth, the University of Notre Dame will host a conference Sunday through Wednesday (Sept. 22-25) celebrating Aquinas’ enduring importance to contemporary cultural, philosophical and theological discussions. “Aquinas at 800: ‘Ad multos annos’” will be the largest conference of its kind, with more than 500 in-person attendees and more than 150 speakers.
- Global leaders discuss ‘What do we owe each other?’ in 2024-25 Notre Dame Forum Inauguration SeriesThe historic Inauguration of Rev. Robert A. Dowd, C.S.C., included a special Notre Dame Forum event on Thursday, Sept. 11, addressing this year’s…