The role of ion-lipid interactions and lipid packing in transient defects caused by phenolic compounds

  • Sheikh I. Hossain
    School of Life Sciences, University of Technology Sydney, Ultimo, NSW 2007, Australia

    School of Chemistry and Molecular Biosciences, University of Queensland, St Lucia, QLD 4072, Australia
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  • Mathilda Seppelt
    School of Life Sciences, University of Technology Sydney, Ultimo, NSW 2007, Australia

    School of Chemistry and Molecular Biosciences, University of Queensland, St Lucia, QLD 4072, Australia
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  • Natalie Nguyen
    School of Life Sciences, University of Technology Sydney, Ultimo, NSW 2007, Australia

    School of Chemistry and Molecular Biosciences, University of Queensland, St Lucia, QLD 4072, Australia
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  • Chelsea Stokes
    School of Life Sciences, University of Technology Sydney, Ultimo, NSW 2007, Australia

    School of Chemistry and Molecular Biosciences, University of Queensland, St Lucia, QLD 4072, Australia
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  • Evelyne Deplazes
    Corresponding author
    School of Life Sciences, University of Technology Sydney, Ultimo, NSW 2007, Australia

    School of Chemistry and Molecular Biosciences, University of Queensland, St Lucia, QLD 4072, Australia
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Published:August 04, 2022DOI:


      The transient disruption of membranes for the passive permeation of ions or small molecules is a complex process relevant to understanding physiological processes and biotechnology applications. Phenolic compounds are widely studied for their antioxidant and antimicrobial properties, and some of these activities are based on the interactions of the phenolic compound with membranes. Ions are ubiquitous in cells and are known to alter the structure of phospholipid bilayers. Yet, ion-lipid interactions are usually ignored when studying the membrane-altering properties of phenolic compounds. This study aims to assess the role of Ca2+ ions on the membrane-disrupting activity of two phenolic acids and to highlight the role of local changes in lipid packing in forming transient defects or pores. Results from tethered bilayer lipid membrane electrical impedance spectroscopy experiments showed that Ca2+ significantly reduces membrane disruption by caffeic acid methyl ester and caffeic acid. As phenolic acids are known metal chelators, we used UV-vis and fluorescence spectroscopy to exclude the possibility that Ca2+ interferes with membrane disruption by binding to the phenolic compound and subsequently preventing membrane binding. Molecular dynamics simulations showed that Ca2+ but not caffeic acid methyl ester or caffeic acid increases lipid packing in POPC bilayers. The combined data confirm that Ca2+ reduces the membrane-disrupting activity of the phenolic compounds, and that Ca2+-induced changes to lipid packing govern this effect. We discuss our data in the context of ion-induced pores and transient defects and how lipid packing affects membrane disruption by small molecules.
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