Intracellular assembly of supramolecular peptide nanostructures controlled by visible light
Yong Ren, Zhixuan Zhou, Iain Harley, Özlem Aydin, Leon Driehaus-Ortiz, Anke Kaltbeitzel, Jiaqi Xing, Konrad Maxeiner, Ingo Lieberwirth, Katharina Landfester, David Y. W. Ng, Tanja Weil
Abstract
Abstract The complex dynamics of synthetic supramolecular systems in living cellular environments impede the correlation between the transient hierarchical species and their biological functions. Achieving this correlation demands a breakthrough that combines the precise control of supramolecular events at discrete time points via synthetic chemistry with their real-time visualization in native cells. In the present study, we reported two peptide sequences that undergo visible light-induced molecular and supramolecular transformations to form various assembly species in cells. In contrast to endogenous stimulus-responsive assembly, the proposed photochemistry enables full control over the photolysis reaction where the monomer generation and local concentration regulate the subsequent assembly kinetics. Phasor-fluorescence lifetime imaging traced the formation of various assembly states in cells associated with monomer activation and consumption, whereas correlative light-electron microscopy revealed the intracellular nanofibres formed. The temporally resolved assembly process shows that the emergence of cytotoxicity correlates with the accumulation of oligomers beyond the cellular efflux threshold.