Designed Multifunctional Spider Silk Enabled by Genetically Encoded Click Chemistry

Abstract

AbstractSpider silk is recognized for its exceptional mechanical properties and biocompatibility, making it a versatile platform for developing functional materials. In this study, a modular functionalization strategy for recombinant spider silk is presented using SpyTag/SpyCatcher chemistry, a prototype of genetically encoded click chemistry. The approach involves AlphaFold2‐aided design of SpyTagged spider silk coupled with bacterial expression and biomimetic spinning, enabling the decoration of silk with various SpyCatcher‐fusion motifs, such as fluorescent proteins, enzymes, and cell‐binding ligands. The silk threads can be coated with a silica layer using silicatein, an enzyme for silicification, resulting in a hybrid inorganic–organic 1D material. The threads installed with RGD or laminin cell‐binding ligands lead to enhanced endothelial cell attachment and proliferation. These findings demonstrate a straightforward yet powerful approach to 1D protein materials.