Surfactins modulate the lateral organization of fluorescent membrane polar lipids: A new tool to study drug:membrane interaction and assessment of the role of cholesterol and drug acyl chain length

D'Auria, Ludovic;Deleu, Magali;Dufour, Samuel;Mingeot-Leclercq, Marie-Paule;Tyteca, Donatienne
(2013) BBA - Biomembranes — Vol. 1828, n° 9, p. 2064-2073 (2013)

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Authors
  • D'Auria, LudovicUCLouvain
    Author
  • Deleu, Magali
    Author
  • Dufour, Samuel
    Author
  • Mingeot-Leclercq, Marie-PauleUCLouvain
    Author
  • Tyteca, DonatienneUCLouvain
    Author
Abstract
The lipopeptide surfactin exhibits promising antimicrobial activities which are hampered by haemolytic toxicity. Rational design of new surfactin molecules, based on a better understanding of membrane:surfactin interaction, is thus crucial. We here performed bioimaging of lateral membrane lipid heterogeneity in adherent living human red blood cells (RBCs), as a new relevant bioassay, and explored its potential to better understand membrane:surfactin interactions. RBCs show (sub)micrometric membrane domains upon insertion of BODIPY (*) analogs of glucosylceramide (GlcCer*), sphingomyelin (SM*) and phosphatidylcholine (PC*). These domains exhibit increasing sensitivity to cholesterol depletion by methyl-β-cyclodextrin. At concentrations well below critical micellar concentration, natural cyclic surfactin increased the formation of PC* and SM*, but not GlcCer*, domains, suggesting preferential interaction with lipid* assemblies with the highest vulnerability to methyl-β-cyclodextrin. Surfactin not only reversed disappearance of SM* domains upon cholesterol depletion but further increased PC* domain abundance over control RBCs, indicating that surfactin can substitute cholesterol to promote micrometric domains. Surfactin sensitized excimer formation from PC* and SM* domains, suggesting increased lipid* recruitment and/or diffusion within domains. Comparison of surfactin congeners differing by geometry, charge and acyl chain length indicated a strong dependence on acyl chain length. Thus, bioimaging of micrometric lipid* domains is a visual powerful tool, revealing that intrinsic lipid* domain organization, cholesterol abundance and drug acyl chain length are key parameters for membrane:surfactin interaction. Implications for surfactin preferential location in domains or at their boundaries are discussed and may be useful for rational design of better surfactin molecules.
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D’Auria, L., Deleu, M., Dufour, S., Mingeot-Leclercq, M.-P., & Tyteca, D. (2013). Surfactins modulate the lateral organization of fluorescent membrane polar lipids: A new tool to study drug:membrane interaction and assessment of the role of cholesterol and drug acyl chain length. BBA - Biomembranes, 1828(9), 2064-2073. https://doi.org/10.1016/j.bbamem.2013.05.006 (Original work published 2013)