Multivalent Clustering of Adhesion Ligands in Nanofiber-Nanoparticle Composites

Because the positioning and clustering of biomolecules within the extracellular matrix dictates cell behaviors, the engineering of biomaterials incorporating bioactive epitopes with spatial organization tunable at the nanoscale is of primary importance. Here we used a highly modular composite approach combining peptide amphiphile (PA) nanofibers and silica nanoparticles, which are both easily functionalized with one or several bioactive signals. We show that the surface of silica nanoparticles allows the clustering of RGDS bioactive signals leading to improved adhesion and spreading of fibroblast cells on composite hydrogels at an epitope concentration much lower than in PA-only based matrices. Most importantly, by combining the two integrin-binding sequences RGDS and PHSRN on nanoparticle surfaces, we improved cell adhesion on the PA nanofiber/particle composite hydrogels, which is attributed to synergistic interactions known to be effective only for peptide intermolecular distance of ca. 5 nm. Such composites with soft and hard nanostructures offer a strategy for the design of advanced scaffolds to display multiple signals and control cell behavior.