Inside the Jellyfish Sting: Exploring the Micro-Architecture of a Cellular Weapon

Summer beachgoers know all too well the painful reality of a jellyfish sting. But how do the stinging cells of jellyfish and their coral and sea anemone cousins ​​actually work? New research from the Stowers Institute for Medical Research uncovers a precise working model for the stinging organelle of the starlet sea anemone, Nematostella vectensis. The study, published online in Nature Communication on June 17, 2022, was led by Ahmet Karabulut, predoctoral researcher in the laboratory of Matt Gibson, Ph.D. Their work involved the application of state-of-the-art microscopic imaging technologies as well as the development of a biophysical model to enable a comprehensive understanding of a mechanism that has remained elusive for over a century. Lessons learned from this work could lead to beneficial applications in medicine, including the development of microscopic therapeutic delivery devices for humans.

The Stowers team’s new model for stinging cell function provides crucial insight into the extraordinarily complex architecture and gating mechanism of nematocysts, the technical name for the stinging organelles of cnidarians. Karabulut and Gibson, in collaboration with scientists from the Stowers Institute Technology Centers, used advanced imagingthree-dimensional electron microscopy and gene silencing approaches to discover that the kinetic energy necessary to pierce and poison a target involved both osmotic pressure and the elastic energy stored in multiple nematocyst substructures.

“We used fluorescence microscopyadvanced and 3D imaging techniques electron microscopy combined with genetic perturbations to understand the structure and functioning mechanism of nematocysts,” Karabulut said.

Using these state-of-the-art methods, researchers characterized the explosive discharge and biomechanical transformation of N. vectensis nematocysts upon firing, grouping this process into three distinct phases. The first phase is the initial projectile-like discharge and targeted penetration of a densely coiled thread from the capsule of the nematocyst. This process is driven by a change in osmotic pressure due to the sudden influx of water and the elastic stretching of the capsule. The second phase marks the unloading and elongation of the wire rod substructure which is further propelled by the release of elastic energy through a process called eversion – the mechanism by which the rod rotates upside down – forming a triple helix structure to surround a fragile inner tubule decorated with barbs containing a cocktail of toxins. In the third phase, the tubule then begins its own eversion process to elongate into the target’s soft tissue, releasing neurotoxins along the way.

“Understanding this complex sting mechanism may have potential future applications for humans,” Gibson said. “This could lead to the development of new methods of therapeutic or targeted drug delivery as well as the design of microscopic devices.”

The entire stinging operation is completed in just a few thousandths of a second, making it one of the fastest biological processes occurring in nature. “The first phase of nematocyst triggering is extremely fast and difficult to capture in detail,” Karabulut said.

As is often the case in basic biological research, the initial discovery was an accident of curiosity. Karabulut embedded a fluorescent dye into a sea anemone to see what it looked like when the nematocyst-rich tentacles were triggered. After applying a combination of solutions to both activate the firing of nematocysts and simultaneously preserve their delicate substructures in time and space, he was shocked to have accidentally captured several nematocysts at different firing stages. .

“Under the microscope, I saw a breathtaking snapshot of discharges of threads onto a tentacle. It was like fireworks. I realized that the nematocysts were partially discharging their threads while the reagent I was simultaneously using and instantly fixed the samples,” Karabulut said.

“I was able to capture images that showed the geometric transformations of the wire during firing in a beautifully orchestrated process,” Karabulut said. “After further examination, we were able to fully understand the geometric transformations of the thread of the nematocyst during its operation.”

Elucidating the elaborate choreography of nematocyst triggering in a sea anemone has interesting implications for the design of artificial microscopic devices, and that collaborative effort between the Gibson Lab and the Stowers Institute Technology Centers may have future applications for human drug delivery at the cellular level.

Co-authors include Melainia McClain, Boris Rubinstein, Ph.D., Keith Z. Sabin, Ph.D., and Sean McKinney, Ph.D.