Understanding the acceptance of spider silk by Schwann cells

Nerve dysfunctions can severely impair the quality of life and successful treatment of peripheral nerve injuries is one of the major challenges in regenerative medicine. An important tool for surgical nerve repair is the use of nerve guidance conduits. These are typically tubes sutured to both ends of the injured nerve to bridge the nerve gap. They support the growth of nerve fibers and cells, especially Schwann cells, which are crucial for nerve regeneration. Longitudinal filaments to fill the hollow conduit structure contribute significantly to improving the outcome of regeneration. We have used spider silk as a natural filament in nerve guidance conduits. Spider silk has peerless properties such as high elasticity and strength and good resistivity to heat. In addition, when used in nerve guidance conduits Schwann cells adhere to spider silks and move along their longitudinal axis. However, spider silk is a natural material with limited availability. Detailed knowledge of spider silk characteristics that support nerve regeneration is important for the development of synthetic fibers that could substitute the silk as an abundant and effective replacement. In this project we will examine the use silks from various spiders to find out which ones can support Schwann cells in cell culture experiments, and what specific material properties account for this cellular support. We will study the chemical, mechanical, structural, and morphological properties of the spider silks in both the dry and wet states of the fibers. This combination of material characterization and silk-cell interactions in culture will help clarify the necessary properties for the success of spider silk. Thus, identifying features that a synthetic material should possess for medical applications. The team working on this project has complementary and interdisciplinary expertise: Prof. Christine Radtke, with long-standing experience in nerve regeneration and nerve guidance conduit implantation, Prof. Helga Lichtenegger, an expert in biomaterials and techniques for structural and mechanical material characterization, and Dr.rer.nat Aida Naghilou, with expertise in spectroscopy, optics, and in vitro cell culture studies of nerve regeneration.

We explored the remarkable properties of spider silk to uncover why it is so effective in supporting nerve regeneration. To this end, we studied silk from a variety of spider species, including golden orb-weavers, jumping spiders, garden-cross spiders, tarantulas, and lynx spiders. Our research revealed that certain types of spider silk significantly enhance the adhesion and migration of Schwann cells, which play a key role in nerve repair. To understand this effect, we examined the material properties of the different silks, including their mechanical strength, protein structure, interaction with water, and microscopic architecture. Using advanced analytical techniques, including synchrotron radiation, lipidomics, proteomics, and RNA-sequencing we were able to study the silk in high detail down to the nanoscale. By relating structure and material properties of silk with the behavior of Schwann cells on each silk type, we gained several important insights. One of our key findings was that not all spider silks are equally good at supporting nerve cells. We discovered that silk from the lynx spider was less effective in supporting Schwann cells attachment compared to silk from golden orb-weavers, jumping spiders, and garden-cross spiders. For the first time, we performed a comprehensive study on the thin lipid layer that naturally coats spider silk. This revealed that the synergy of the lipid coat on the silk surface and its protein structure plays a crucial role in how well Schwann cells can attach to the fibers. We also showed that the mechanical properties of silk, meaning how stiff or flexible it is, are directly linked to its protein structure, and these features strongly influence how fast and how directed the movement of Schwann cells is. This was a crucial discovery, as we found that a type of silk that has so far received little attention is best at supporting rapid Schwann cell migration. We also saw that some silks from the cocoon of spiders naturally have small grooves running along their surface, similar to microscopic pathways. We demonstrated that these grooves guide the cells, helping them move faster and in a more directed way. Our findings are essential for creating future novel biomaterials for application in nerve repair. By understanding what makes natural spider silk so effective, we can design new silk-inspired materials that are easier to produce and control, are more accessible in large amounts, and yet still capable of supporting nerve regeneration to the extent that the native silk does. Such materials could open new possibilities for biomedical applications and guide and accelerate the healing process.