Hierarchical Growth of Fluorescent NanoStructures in Live Cells – HiOF

The programmable bottom-up growth of bioactive artificial nanostructures in live cells, which can be visualized and tracked in real-time, is a tremendous modern challenge which requires to master a) the hierarchical self-assembly processes across scales, b) the specific targeting in complex environments such as living cells, and c) the correlation of nanostructure growth with emerging bioactivity. The HiOF project will explore a chemical system where fluorescent & bioactive nanostructures emerge spontaneously in specific cellular compartments (e.g. plasma membranes, mitochondria, lysosomes, and endoplasmic reticulum), as a result of a hierarchical process involving dual targeting and dynamic covalent self-assembly of fluorescent aromatic compounds with modified peptides, followed by their supramolecular polymerization. Specifically, the project aims at developing structure-activity relationships that enable programming the organelle-targeting and self-assembly of intrinsically-fluorescent & photoactive nanostructures, simply by mixing appropriate and complementary molecular building blocks directed to specific organelles. The systems will be studied in solution, then in model membranes and, finally, in live cells. Finally, we will explore the capability of the nanostructures to photo-induce programmed cell death (apoptosis) by generating singlet oxygen in specific cellular compartments. The HiOF project will represent a fundamental breakthrough from which biological/therapeutic applications will ensue given the high versatility and ease of functionalization.