Manipulating amyloid self-assembly: toward the design of functionalized proteinaceous nanostructures

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Endogenous proteins are known for their ability to self-associate in living organisms into supramolecular structures that perform vital physiological functions. Over the last decade, amyloid structures that accomplish crucial biological activities have been identified in almost all species, from bacteria to mammals. Amyloids are highly organized proteinaceous assemblies that are characterized by a cross-beta-sheet quaternary conformation in which individual beta-strands are running perpendicular to the fibril axis. The mechanical, physical and biological properties of amyloids suggest that they hold great potential as nanomaterials for (bio)technological applications. For instance, amyloid based-materials were recently evaluated as scaffold for cell growth, drug delivery systems and nanosensors. Despite their tremendous potential as functional advanced soft materials, the usage of amyloids in nanomedicine and nanotechnology is still today limited by a number of issues, which include; (i) incomplete understanding of the mechanisms of self-assembly, (ii) difficulty to control amyloid formation and (iii) challenge to predict the supramolecular architecture from the peptide sequence. In this context, the overarching goal of this research program is to uncover innovative strategies to manipulate peptide self-assembly and to construct highly ordered functionalized proteinaceous nanostructures. Toward this goal, the three following specific aims will be addressed: 1. Identify strategies to modulate the (supra)molecular architecture of peptide assemblies 2. Conceive chemical approaches to probe and temporally photocontrol amyloid formation 3. Implement chemoselective methods to orthogonally functionalize proteinaceous nanostructures Life-inspired protein assemblies, including amyloids, have recently received a huge increase of interest for the design of supramolecular structures. This research program will lead to novel strategies to construct functional proteinaceous nanostructures and will contribute to the fundamental knowledge of amyloid formation. By studying the roles of conformational and physicochemical properties in molecular self-assembly, we aim at fine-tuning the amyloid suprastructure with a precise design at the molecular level. By developing conformational-sensitive probes and photoresponsive elements, we will support a better understanding of the driving forces that kinetically control assembly. Overall, this program will transform the perception of the scientific community towards these fascinating nanostructures, fostering the applications of functional amyloid-based advanced biomaterials. Accordingly, this program will open to novel research opportunities and innovative applied avenues for Canada's nanotechnology, life sciences and biopharmaceutical sectors.