Controlled Transport of Cell-penetrating Peptides across Biological Membranes – Synergy of Simulations and Single Molecule Fluorescence Experiments

The controlled transport of cargo into cells is vital for life-sustaining. Alongside the active ATPdriven process of endocytosis, which plays a pivotal role in the transport of cargo across membranes, there is another promising method known as direct passive energy-independent translocation, which is particularly relevant for controlled drug delivery. Short, positively charged cell penetrating peptides (CPPs) are commonly utilized vectors for this purpose. This proposal seeks to explore the mechanism of passive translocation of CPPs at the molecular level through advanced molecular simulations aided by complementary single-molecule fluorescence experiments performed in the co-applicant institution. Our focus will be on understanding crucial steps in this process, including adsorption, aggregation, and translocation across advanced model membrane systems. The insights gained from this investigation will lay the groundwork for designing smarter drug delivery systems by identifying crucial molecular interactions during the transport of matter across biological membranes.