How lipid asymmetry influences membrane protein function

• Applicant: Professor Dr. Daniel Huster
• Subject Area: Biophysics
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 546534953

Despite the inherent asymmetry in eukaryotic and prokaryotic plasma membranes, characterized by distinct lipid compositions across their two leaflets, the predominant majority of both experimental and computer simulation studies of membrane systems utilize symmetric bilayers. This project aims to bridge this critical research gap through a synergistic approach that combines molecular dynamics simulations, solid-state NMR spectroscopy, and scattering techniques. Our aim is to elucidate the structural and dynamic properties of lipid molecules in asymmetric membranes, emphasizing their interactions with integral membrane proteins. We propose to study essential membrane properties in various asymmetric bilayer models with an emphasis on bacterial lipid composition. We will measure leaflet-specific lipid chain order parameter, lipid dynamics, characterized by correlation times of motions and motional amplitudes, bilayer structure etc. We will also focus on lipid-protein interactions and study membrane-induced effects and the enzymatic activity on the two bacterial proteins OmpLA and GlpG, representing the two canonical types of membrane protein architecture, β-barrel and α-helical transmembrane proteins, in asymmetric membranes. We expect fundamental insight into the specific importance of lipid asymmetry in biological membranes and its influence on membrane protein function. The obtained understanding has potential for pharmaceutical and biotechnological applications, such as the development of lipid-targeted therapeutics and biosensors, whose activities will be modulated by specific lipid leaflet compositions.

• DFG Programme: Research Grants
• International Connection: Austria, Czech Republic
• Partner Organisation: Czech Science Foundation; Fonds zur Förderung der wissenschaftlichen Forschung (FWF)
• Cooperation Partners: Professor Dr. Georg Pabst; Professor Dr. Robert Vacha