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Passive membrane transport of organic compounds

Final Report Summary - PASSMEMBRANE (Passive membrane transport of organic compounds)

The transport of small molecules into and out of living cells is a ubiquitous phenomenon in nature. Cells need to tightly control the uptake of nutrients while pumping out metabolic waste products. Sophisticated machines, so-called membrane proteins, located in the cell membrane are taking care of these complex tasks. However, a full understanding of the physical mechanism is still elusive. In this project we investigated the fundamental principles that govern the passive transport of nutrients and drug molecules through cell membranes. In a two pronged approach we developed a system that allows building an artificial membrane protein based on the combination of small water channels, optical tweezers and colloidal particles while studying transport of drug molecules through lipid membranes and natural protein channels.
We are investigating the relevance of direct transport of molecules through the cell membrane without the help of protein transporters. Our results show that small organic molecules can freely diffuse through the cell membranes and more importantly can fundamentally change cellular functions. This is especially relevant for the communication of bacteria and eukaryotic cells in the human gut. We showed that bacteria can change the expression of hormones using indole and thus could influence human metabolism directly. We also discovered that indole is secreted in a brief pulse that in part of the important control systems that control the growth of bacteria in environments with limited resources.
With the help of our novel system for protein channels we were able to demonstrate that cells optimize the passive transport through proteins by building dedicated proteins for each nutrient. With our unique and fully controlled system we tested theoretical models for membrane transport. Our results will help in the development of a complete and quantitative description of membrane transport in general. Our will guide the design of novel drug molecules that are more efficiently transported into cells and thus increase the efficacy of the treatment.
In parallel, we developed a novel way to create artificial membrane proteins build from DNA origami. We used these structures to control molecular motion by designing DNA origami nanopores that mimic protein functions. We could also show that these pores can be incorporated into lipid membranes and thus open a pathway to build artificial membrane proteins that might find applications in nanomedicine for drug delivery as well as treatment for disease.