Supramolecular Engineering of biologically iNSpired peptide nanostructurEs

ongoing

To date, the main efforts for the design of bioactive self-assembled 1D nanostructures have been focused on the use of static assemblies. The development of synthetic systems with inherently stimuli-responsive behavior will open new possibilities for the creation of artificial architectures that mimic the natural protein nanostructures found in eukaryotic cells, which are dynamic, and capable of rapid growth or disassembly to tune their properties, and thus adapt to the cell needs. SENSE aims to: 1) Define robust peptide-based building blocks, and implement stimuli-responsive interactions between them to engineer complex self-assembled responsive nanostructures. 2) Modify these dynamic platforms to achieve precise nanoscale control over the presentation of bioactive molecules in the final multivalent nanostructures. 3) Apply these responsive and multivalent nanostructures as smart delivery vehicles and improved bioactive scaffolds. 4) Integrate them into living cells as artificial adaptor nanostructures that can present multiple signaling elements for controlling cell behavior. Taken together, the objectives of SENSE will define a new multidisciplinary approach combining organic, peptide, supramolecular and dynamic covalent chemistries, and nanotechnology for the development of adaptive materials that rely on dynamic interactions, and are therefore ideally suited to interfacing with living organisms. During my career I have acquired the singular background that combines chemistry, chemical biology, and nanotechnology required to achieve the objectives of SENSE. Particularly relevant to this project is my experience in peptide synthesis and their modification, as well as in the preparation of supramolecular peptide-based materials and the study of their properties in living cells.