ABSTRACT

Hagfish slime threads form the fibrous fraction of the defensive slime of hagfishes. The threads develop within specialized cells within the slime glands and consist of a dense bundle of the cytoskeletal elements known as intermediate filaments. The threads leave the hagfish’s body in a condensed state, but quickly unravel into fine protein strands that are more than 10 cm long and approximately 2 µm in diameter. The proteins that make up the threads are dominated by α-helical secondary structure, but when acted upon by an external force, they stretch and adopt structures dominated by β-sheets. In this state, slime threads exhibit Congo red metachromasia and birefringence. These stretch-transformed threads differ from conventional amyloids in several ways. Most importantly, strands within β-sheets run parallel to the fibre axis, unlike the cross-β arrangement in typical amyloid fibrils. This arrangement means that stretched slime threads possess little in the way of “hidden length”

or “sacrificial bonds” and as such are quite stiff, without an obvious yield point. The study of hagfish slime thread mechanics has led to unexpected insights into the function of intermediate filaments in other systems, including the cytoskeleton of live cells and α-keratins. Although amyloid-like structures only appear in slime threads outside of the animal’s body, it is possible that exceptional mechanical stresses could lead to amyloid-like structures within cells, with potential consequences for the development of conformational disease.