The role of cholesterol in membrane activity of digitonin: Experimental and theoretical model studies

• Published in: Journal of molecular liquids Vol. 323; p. 114598
• Main Authors: Korchowiec, Beata, Janikowska-Sagan, Maria, Kwiecińska, Klaudia, Stachowicz-Kuśnierz, Anna, Korchowiec, Jacek
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01-02-2021
• Subjects: Digitonin-cholesterol interaction; Langmuir films; Lipid monolayers; Molecular Dynamics; Saponin; Lipid monolayers; Molecular Dynamics; Langmuir films; Digitonin-cholesterol interaction; Saponin
• ISSN: 0167-7322; 1873-3166
• DOI: 10.1016/j.molliq.2020.114598

Molecular insight into the digitonin-sterol interaction is essential for potential membrane-associated digitonin applications, including cancer treatment, membrane lysis and membrane transport. Here, interactions of digitonin with monolayers of cholesterol and diosgenin were investigated with the use of Langmuir monolayer techniques, classical dynamics simulation and quantum chemistry methods. The results obtained show that digitonin penetrates and effectively incorporates into sterol monolayers, changing the fluidity of monolayers and lipid arrangement. Both cholesterol and diosgenin form stable complexes with digitonin molecules. Almost all identified complexes were formed via hydrogen bonds between lipid headgroup oxygen atoms and headgroup hydroxyl groups of digitonin. The calculated stabilization energies were greater for diosgenin/digitonin complexes, which was attributed to electrostatic interactions between polar atoms in the hydrophobic parts of both molecules.
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•Digitonin has a high affinity for both cholesterol and diosgenin monolayers.•The incorporation of digitonin into the lipid monolayers has a destabilizing effect on the system.•Stable complexes are formed between digitonin and cholesterol or diosgenin.•The complexes are stabilized by hydrogen bonds and electrostatic interactions.