Biocatalytic Regulation of Peptide Self-Assembly for Biomineralization.

The production of functional hierarchical architectures through the biomineralization of a continuously secreted protein matrix is prevalent in nature; however, it remains challenging to mimic this dynamic aspect of the biomineralization process, especially in biological systems. Here we report the use of dynamically generated supramolecular assemblies of peptides for in situ biomimetic mineralization in live cells. Specifically, by integrating enzymatic regulation of inorganic phosphate concentration and enzyme-instructed self-assembly, we demonstrate a phosphorylated tripeptide that self-assembles into dynamic supramolecular nanofibers via enzymatic dephosphorylation to template biomineralization with the inorganic phosphate. This biomimetic mineralization results in the formation of peptide-inorganic hybrid nanocrystals, with tunable crystal size and calcium-to-phosphorus (Ca:P) ratio, regulated by enzyme activity. Cellular enzymes can instruct in situ biomineralization around mammalian cells, inducing cell aggregation and osteogenic differentiation. This work presents a novel strategy for mimicking the dynamic biomineralization of a protein matrix and regulating biomimetic mineralization in live cells to control the cell fate.