Biophysical interaction mechanisms of statins with model lipid membranes: interfacial composition, structure and dynamics
Statins are commonly used therapeutic agents for cardiovascular diseases and lipid disorders that lower the LDL cholesterol level. Our recent Langmuir studies have shown that pravastatin, fluvastatin and cerivastatin influence the properties of lipid monolayers at the air-water interface and the observed fluidizing effects are related to the interaction in the headgroup region. However, direct information about the composition, structure and dynamics of statins in lipid monolayers at the air-water interface is still missing. Therefore, we propose 3 days of beam time on FIGARO to acquire quantitative information on the three statins with DMPC and DMPS monolayers representing key lipid characteristics of intestinal cell membranes. Structural measurements will allow us to resolve the changing location of the drug in the model membrane with varying drug hydrophobicity and lipid headgroup charge. Dynamic compositional measurements will provide novel quantitative information about the relative extents of such interactions and lipid loss from the interface. These results can significantly enhance our understanding of the molecular interactions important in the view of future drug design.
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Richard A. Campbell; Glenn J. Coope; GUTFREUND Philipp; Armando Maestro; MATYSZEWSKA Dorota and ZABOROWSKA Michalina. (2021). Biophysical interaction mechanisms of statins with model lipid membranes: interfacial composition, structure and dynamics. Institut Laue-Langevin (ILL) doi:10.5291/ILL-DATA.9-13-1001
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