Studying lipid membrane dynamics: challenges and potentials of super-resolution microscopy

Christian Eggeling

Professor of Super-Resolution Microscopy, Institute of Applied Optics and Biophysics, Friedrich‐Schiller‐University & Leibniz Institute of Photonic Technology e.V., Jena, Germany

Molecular interactions are key in cellular signalling. They are usually ruled by the organization and mobility of the involved molecules such as lipids in membranes. However, the direct and non-invasive observation of the interactions of lipids in the living cell membrane is often impeded by principle limitations of conventional far-field optical microscopes, for example with respect to limited spatio-temporal resolution and information content. Here, we present super-resolution microscopy studies involving tools such STED(-FCS) microscopy in combination with spectral imaging and fluorescence correlation spectroscopy or single-molecule tracking on a MINFLUX and interferometric Scattering (iSCAT) microscope. We highlight how these approaches can reveal novel aspects of lipid membrane bioactivity such as of the existence and function of potential lipid rafts and during pathogen invasion, but also where they reveal limitations.