Silk Road Revealed: Mechanism of silk fibre formation inBombyx mori

Abstract Silk fibroin (SF) is one of the most exploited and studied natural materials, yet the complex sequence of dynamic transitions required to transform from a liquid state to a solid fibre remain unresolved. We found that fibroin heavy chain (FibH) from Bombyx mori ( B. mori ), a multidomain protein with highly repetitive domains, folds to form β-solenoid structures. The single fibroin molecule undergoes conformational transformations from a globular form to an extended solenoid driven by pH reduction. Following this, the N-terminal domain (NTD) drives higher-order oligomerisation beyond the proposed biological tetrameric unit when in the extended state. 1,2 The proposed supramolecular structures explain the complex rheological behaviour observed for silk and the liquid crystalline textures observed within the B. mori gland. Overall, our results demonstrate that silk assembly is a highly organised process, where a mild reduction in pH promotes molecular reorganisation and higher-order oligomerisation of the N-terminal domain into structures that precede fibre formation. Moreover, we suggest that NTD is at least partially hydrolysed and lost during the standard regeneration/reconstitution processing, explaining the historical differences between native and regenerated feedstocks. We believe our results expand our understanding of the liquid-to-solid transformation of fibroin molecules, as well as indicate to other researchers a clear strategy to determine the quality of their feedstock, which can be translated into improved materials fabrication.