Enzymatically-active nanoparticles to direct the self-assembly of peptides in hydrogel with a 3D spatial control

Hydroxypropylmethylcellulose grafted with silanol groups (Si-HPMC) hydrogels are employed as 3D scaffolds to encapsulate phosphatase-modified silica nanoparticles (AP@NPs). Such hybrid materials are catalytically active when enzyme susbtrates are diffusing through the material. Using the enzyme-assisted self-assembly concept, the tripeptide Fmoc-FFY is generated in situ in close vicinity of AP@NPs thanks to the phosphate hydrolysis of the diffusing precursor Fmoc-FFpY. The self-assembly of Fmoc-FFY is spatially concomitant to the presence of AP@NPs. In the Si-HPMC host hydrogel, AP@NPs aggregate and thus limit their diffusion in the material. This feature is used to localize at the micrometre scale the self-assembly within the material: AP@NPs are injected in a defined 3D area within the Si-HPMC gel using an adapted microsyringe. The diffusion of precursor Fmoc-FFpY toward this region leads to a Fmoc-FFY self-assembly exclusively there, an impossible strategy using free AP. Thus, this work allows to spatially control the enzyme-assisted self-assembly of peptides within host materials as an alternative approach for the design of hierarchically structured materials.