Supramolecular Tandem Membrane Assays

• Applicants: Professor Dr. Andreas Hennig; Professor Dr. Werner Nau
• Subject Area: Biological and Biomimetic Chemistry ; Biochemistry ; Organic Molecular Chemistry - Synthesis and Characterisation
• Term: since 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 467446229

Membrane transport of organic molecules plays a crucial role in the discovery and delivery of small-molecule drugs as well as in the mechanism of action of antimicrobial peptides and cell-penetrating peptides (CPPs). It still remains, however, a major experimental challenge to measure the actual transport of these compounds across the lipid bilayer membrane. We have recently shown that liposome-encapsulated supramolecular reporter pairs excellently qualify to unambiguously detect membrane transport of organic molecules and peptides by a simple and fluorescence-based method. Within this project, we want to further establish the utility and applicability of this method.Therefore, we will encapsulate supramolecular reporter pairs in liposomes of varying size and membrane composition, and we will investigate the membrane transport of selected organic molecules and peptides by absorption and fluorescence spectroscopic methods. This includes spectroscopic characterisations, time-resolved measurements including stopped-flow techniques for rapid kinetics, as well as fluorescence microscopy with giant uni-lamellar vesicles (GUVs).We will further develop these “supramolecular tandem membrane assays” by applying them to follow membrane transport of small, unlabeled molecules and CPPs. In detail, we plan to establish multicolor methods for mechanistic investigation of membrane transport processes, measure fast efflux kinetics, and we will combine tandem membrane assays with enzymatic reactions to provide new avenues for the development of supra-biomolecular sensor systems.

• DFG Programme: Research Grants