Metal-Coordinated Assembly of Collagen-like Proteins into Microflorettes

Collagen is the most abundant protein in the extracellular matrix. Owing to its exceptional biocompatibility, collagen-based materials are widely utilized in biomedicine. Genetic engineering enables the production of collagen derivatives tailored to biomaterial applications. Herein, we engineered a stimulus-responsive system to regulate the supramolecular assembly of collagen-like proteins (CLPs). By introducing histidine (His) residues, we achieved metal-mediated coordination driving distinct three-dimensional (3D) architecture formation. Dynamic light scattering analysis confirmed aggregation upon the addition of Zn(II), while scanning electron microscopy (SEM) revealed their morphologies. Notably, the positioning of His residues governed the assembly morphology, with variants bearing terminal His-tags forming reticular networks and those with central residues yielding microflorette-shaped assemblies. Biological assessments demonstrated that these CLPs exhibit negligible cytotoxicity and support cell adhesion and migration comparable to natural collagen. Consequently, these proteins hold significant promise for drug delivery and regenerative medicine.