Identification of peptides with targeted adhesion to bone-like mineral via phage display and computational modeling

Abstract

The challenges in engineering bone scaffolds reflect the complexity of bone as an organ. The organic-inorganic hybrid system design aims to provide signals within a conductive apatite layer to promote cell adhesion, proliferation and ultimately differentiation into bone tissue. Dual functioning peptides designed to specifically adhere to the apatite layer, while promoting cell adhesion via cell recognition sequences, may increase cell adhesion, leading to increased osteogenesis. The aim of this study is to identify peptide sequences with preferential adsorption towards apatite-based materials. Bone-like mineral films and hydroxyapatite disks were panned with a phage library to elucidate peptide sequences with favorable adsorption. Peptide sequences were analyzed using the web-based biotechnology tool RELIC and validated with a modified ELISA, in addition to being investigated using a newly developed method of high-throughput computational modeling. Peptides having the highest affinity and greatest potential to be incorporated into a dual functioning peptide design are APWHLSSQYSRT, VTKHLNQISQSY and STLPIPHEFSRE. These experiments provide a method of rationally designing peptides that adhere to apatite and that may improve bone tissue regeneration. This work also provides structure for investigating peptide/protein adsorption on apatite substrates with varied carbonate, or other impurity, content.