Development of bioactive peptide matrices: from molecular structure to biomedical applications

Abstract

This Project aims to produce and characterize nanostructured scaffolds based on the self-assembly of peptides belonging to three major classes of bioactive compounds: cell-penetrating peptides (CPPs), constituents of the extracellular matrix (ECM), and anti-inflammatory peptides (AIPs). The supramolecular architectures investigated here are original, and their bioactive characteristics open perspectives for developing unprecedented biomedical materials. Our quest will be focused on understanding the self-assembly pathway of these matrices, their supramolecular properties, and their cell responses in vitro. The CPPs will be either derived from viral proteomes or related to the family of Transportan peptides, whereas the ECM constituents will be inspired by elastin-like sequences containing the RGD motif. The AIPs will be based on tetrapeptides derived from the thymosin-b4 protein, a major cellular constituent with a key role in tissue regeneration. A set of cutting-edge structural techniques involving advanced spectroscopic methods, cryogenic electron microscopy (cryo-EM), and small-angle X-ray scattering (SAXS and SANS) will be used to provide detailed information on the supramolecular organization of these systems. In addition to these advanced structural analyzes, cell assays will be conducted to determine if bioactivity displayed by the molecular building blocks is affected upon organization into superstructures. In the end, we expect to establish structure-activity relationships and contribute to optimizing the formulation of biomedical materials based on these bioactive molecules. (AU)