Lipid Nano-clustering by external stimuli
Prof. Dr. Heiko Heerklotz1 and Jun. Prof. Dr. Winfried Römer2
1 Faculty of Chemistry and Pharmacy, Institute of Pharm. Sci., University of Freiburg
2 Faculty of Biology, Institute of Biology II, University of Freiburg
Nanoscale membrane dynamics play a vital role in various cellular processes. For example, the clustering of host cell glycolipids by lectins is sufficient for inducing the cellular uptake of toxins, viruses, and bacteria. Electrostatic clustering of, e.g., anionic membrane lipids by polycationic solutes like peptides and synthetic polymers may cause membrane leakage and other changes in membrane structure and function.
The primary objective is to jointly accomplish a much more comprehensive understanding of the general effects of clustering on the activity and selectivity of membrane-binding molecules. The final aim is to generalize the insights from the different cases, methods, and perspectives to establish a general concept of lipid nano-clustering, recognizing its prerequisites and predicting its functional consequences. The project utilizes and further develops the methodologies of the two labs. These are mainly: isothermal titration calorimetry (binding, possibly also clustering), differential scanning and pressure perturbation calorimetry (demixing), time-resolved fluorescence (membrane packing, leakage, etc.), cryo-transmission electron microscopy (nanoscopic, structural effects), confocal fluorescence microscopy (clustering kinetics, membrane curvature and order), and atomic force microscopy (nanoscale-clustering, phase-separation, membrane rearrangements and stiffness). Synthetic lipid systems (small and giant unilamellar vesicles, supported lipid bilayers) will are chosen to test the correlation between clustering and membrane curvature as well as raft-like domain formation.