A jellyfish can close a wound in real time, without stitches, scabs, or scars, a fascinating—and borderline miraculous—healing ability that has long perplexed scientists.
Now, a new study in Molecular Biology of the Cell has finally revealed the secrets behind this process, identifying two cellular structures that act in a specific sequence.
Jocelyn Malamy, an associate professor at the University of Chicago, first observed this process a decade ago at the Marine Biological Laboratory. Using transparent, dime-sized jellyfish called Clytia hemisphaerica, she watched individual cells move toward each other to close a gap in the tissue.
Now, with colleagues Maxwell Sassaman and Manjula P. Mony, she has mapped the steps of this process and explored its broader significance.
A Flower That Never Stops Blooming
The free-swimming medusa most people picture when they hear “jellyfish” is only one phase of Clytia‘s life. It spends most of its life as a polyp colony attached to rocks, docks, or leaves, and it periodically produces medusae, much like a shrub produces flowers. While medusae live for only a few months, the polyp colonies can persist for much longer.
Clytia medusae are known for their ability to heal quickly. Small wounds close in minutes, and even larger injuries seal in under an hour, all without forming scar tissue. Malamy notes that this type of healing is similar to the scar-free repair seen in embryos.
Since Clytia are transparent, heal rapidly, and lack the immune-mediated inflammation that complicates wound healing in mammals, they serve as an excellent model organism. Scientists can watch epithelial cells close wounds in real time, without interference from scarring or immune reactions. The mechanisms uncovered in Clytia are likely relevant across many animals.
“A lot of the processes that we see in Clytia‘s wound healing are really similar to what you see in all other systems, including mammalian systems,” Malamy explains. “When you’re staring at these epithelial cells, you wouldn’t know this was a jellyfish.”
Two Structures, One Decision Tree
Epithelial cells form the surfaces of the body, including skin, the gut, and internal membranes, and must repair themselves after injury. Malamy previously described Clytia’s wound repair in 2017 and 2018. The new study addresses a longstanding question in epithelial wound healing: do wounds close by cells moving over the gap, or by an actin cable contracting to seal it? The findings show that both mechanisms operate in a specific sequence, with the basement membrane beneath the cells coordinating the transition between them.
The initial response involves lamellipodia, actin-rich extensions that move across the basement membrane, the protein layer beneath all epithelial tissues. These structures pull their parent cells forward to close the wound. Malamy’s team observed lamellipodia forming even in very small wounds within a single cell, a previously undocumented detail.
After the lamellipodia advance, an actomyosin cable forms and contracts after it covers the basement membrane. If damage or debris blocks the membrane, the cable closes the wound and removes debris that lamellipodia cannot cross.
For larger wounds, a third response occurs. When the gap is too wide for lamellipodia to bridge, regardless of how far the cells extend, the entire epithelial sheet lifts and migrates as a unit. Once lamellipodia from opposing edges meet, the same closing sequence resumes.
“This is a truly elegant mechanism where the system can rapidly adapt to heal all the kinds of wounds that might occur in nature,” Malamy says.
What’s Still Unrepaired
If epithelial repair mechanisms are conserved across animal evolution, as current evidence suggests, studies of jellyfish could reveal wound-healing processes that inflammation and scar formation obscure in mammals, making those processes difficult to observe directly.
Researchers have not yet fully understood the basement membrane, which coordinates these processes, and it remains the least understood aspect of wound repair. Scientists still do not know how organisms repair the basement membrane itself.
“It’s great that you can heal a wound by dragging the cells over it,” Malamy says, “but at some point, a damaged basement membrane has to get fixed.” That’s her next target.
Austin Burgess is a writer and researcher with a background in sales, marketing, and data analytics. He holds an MBA, a Bachelor of Science in Business Administration, and a data analytics certification. His work focuses on breaking scientific developments, with an emphasis on emerging biology, cognitive neuroscience, and archaeological discoveries.