When our skin is injured, a complex process begins to heal the wound. Keratinocytes, the cells that form the outer layer of the skin, move together to close the wound. However, researchers have discovered that the protein PIEZO1 can interfere with this process, slowing down wound healing. Understanding PIEZO1's role in cell movement could lead to new methods to improve wound healing, which would benefit many people with chronic injuries and wounds.
Researchers at the University of California, Irvine, have discovered a critical role for the ion channel PIEZO1 in regulating cell migration during wound healing. The study, led by Professor John Lowengrub and Dr. Medha Pathak along with Dr. Jinghao Chen, Dr. Jesse Holt and Dr. Elizabeth Evans, was published in the journal PLOS Computational Biology. The research reveals how PIEZO1 inhibits the formation of leader cells, which are essential for coordinated cell migration, thereby affecting the wound healing process.
Leader cells, which form at the wound edge, transmit mechanical and biochemical signals that coordinate the movement of follower cells to close the wound. The researchers used a combination of experimental methods and mathematical models to investigate the role of PIEZO1 in this process. Their findings indicate that PIEZO1 activity suppresses the formation of these leader cells, leading to a less organized and slower wound closure.
Dr. Chen explained the motivation for the study: “Understanding how PIEZO1 regulates the formation and coordination of leader cells during keratinocyte migration provides valuable insights into the mechanisms underlying wound healing. Our findings suggest that targeting PIEZO1 could improve wound healing efficiency.”
Using time-lapse microscopy and scratch wound assays, the team observed that PIEZO1 activity increased cell retraction along the wound edge, inhibiting the advancement of cells required for wound closure. The experiments showed that cells lacking PIEZO1 had more leader cells and therefore more efficient wound closure compared to cells with normal or increased PIEZO1 activity.
The research team also developed a new two-dimensional continuum model of wound closure, incorporating key factors such as cell motility, retraction, cell-cell adhesion, and coordinated directionality. This model allowed them to simulate the effects of PIEZO1 on collective cell migration and validate their experimental findings. Their simulations confirmed that increased PIEZO1 activity leads to decreased coordinated directionality, which inhibits efficient wound closure.
Dr. Chen highlighted the importance of his findings: “Our study provides a comprehensive framework for understanding the biophysical mechanisms by which PIEZO1 regulates collective cell migration. This knowledge could inform the development of new therapeutic strategies to improve wound healing.”
In summary, the research highlights the importance of mechanical signals in wound healing and offers a potential target for therapeutic intervention. The insights of Professor Lowengrub, Dr Pathak and their team into the role of PIEZO1 in the formation and coordination of leader cells during keratinocyte migration pave the way for future research into improving wound healing processes.
Journal reference
Chen, J., Holt, JR, Evans, EL, Lowengrub, J.S., & Pathak, MM (2024). PIEZO1 regulates leader cell formation and cellular coordination during collective keratinocyte migration. PLOS Computational Biology. DOI: https://doi.org/10.1371/journal.pcbi.1011855
About the author
Jinghao Chen He recently received his PhD in Mathematics from the University of California, Irvine in 2024, under the supervision of Professor John Lowengrub. His primary research interests lie in the domain of computational and applied mathematics, with a strong focus on mathematical biology. Within this field, he develops mathematical models incorporating appropriate partial differential equations to effectively capture and study a wide range of biological patterns and phenomena. Jinghao’s work has been funded by multiple grants and awards, and he has presented his findings at several international conferences.
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