The Matthies lab is interested in the structure and function of membrane protein complexes in their native lipid membrane environment to understand their mechanism and the influence of the immediate surrounding in human health and disease. A cell contains many different lipid membranes with various lipid contents and distributions which are very important for a membrane’s morphology and function but very little is understood on how these various micro-environments are formed, maintained and how they influence the structure and function of membrane proteins. Studying membrane protein complexes in their native biological membrane is therefore required.
We use a combination of molecular biology, biochemistry and biophysical methods to study molecular transport across membranes with a focus on how the immediate native environment influences the structure and function of membrane proteins, but also how proteins and lipids shape and functionalize a lipid membrane.
Cryo-Electron Microscopy (Cryo-EM) is one of the main structural biology methods of the lab. We solve high-resolution structures of membrane proteins in artificial environments such as detergent micelles and lipid nano-discs using Single-Particle Cryo-EM, but we are extending this approach to studying membrane proteins in their native environment using native lipid nano-discs, membrane fractions in forms of vesicles, and intact cells and tissues using a combination of Correlative Light and Electron Microscopy techniques, including Cryo-Fluorescent Microscopy, Cryo-Focused Ion Beam-Scanning Electron Microscopy (Cryo-FIBSEM), Cryo-EM and Cryo-Electron Tomography (Cryo-ET).
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Banner image: The eukaryotic cell with its organelles and various membranes (Image credit: Veronica Falconieri Hays).