Controlled Supramolecular Assembly Inside Living Cells by Sequential Multistaged Chemical Reactions
Michaela Pieszka, Shen Han, Christiane Volkmann, Robert Graf, Ingo Lieberwirth, Katharina Landfester, David Y. W. Ng, Tanja Weil
Abstract
Synthetic assembly within living cells represents an innovative way to explore purely chemical tools that can direct and control cellular behavior. We use a simple and modular platform that is broadly accessible and yet incorporates highly intricate molecular recognition, immolative, and rearrangement chemistry. Short bimodular peptide sequences undergo a programmed sequence of events that can be tailored within the living intracellular environment. Each sequential stage of the pathways beginning with the cellular uptake, intracellular transport, and localization imposes distinct structural changes that result in the assembly of fibrillar architectures inside cells. The observation of apoptosis, which is characterized by the binding of Annexin V, demonstrates that programmed cell death can be promoted by the peptide assembly. Higher complexity of the assemblies was also achieved by coassembly of two different sequences, resulting in intrinsically fluorescent architectures. As such, we demonstrate that the in situ construction of architectures within cells will broaden the community's perspective toward how structure formation can impact a living system.