Summary
The defensive slime of hagfishes contains thousands of intermediate filament protein threads1 that are manufactured within specialized gland thread cells2–4. The outstanding material properties of these threads, which rival spider dragline silks, make them an ideal model for biomimetic efforts to produce sustainable protein materials5. The gland thread cell is remarkable because of the strength of the thread it produces, but also because of the thread’s impressive length (~150 mm)1, its exquisite packaging within the cytoplasm3,4, and its ability to deploy rapidly in seawater without tangling6. The thread bundle (or “skein”) is organized into staggered loops that spiral around the long axis of the cell. In mature cells, these highly organized loops fill most of the cell volume. Although the exact site of thread assembly is unknown, the thinnest regions of the thread are found adjacent to the nucleus7,8. Intermediate filaments and microtubules are known to interact during early stages of thread assembly, but the mature thread is electron dense with no discernable ultrastructure7,8. Until now, we have lacked information about gland thread cell development, including high power images of very young cells that could provide insight into how the thread is coiled and how it matures. Here we show (1) how changes in nuclear morphology, size, and position can explain the three-dimensional pattern of thread coiling in gland thread cells, and (2) how the ultrastructure of the thread changes from very young thread cells up to large cells with fully mature skeins7–9. Our model provides an explanation for the complex process of thread assembly and organization that has fascinated and perplexed biologists for over a century10, and provides valuable insights for the quest to manufacture high-performance biomimetic protein materials.